bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Nanotechnology in Overcoming the Multidrug Resistance in Cancer Therapy: A Review
Authors: Mir Suhail Ahmad , Hamid Laraibah , Bader Ghulam Nabi , Shoaib Ambreen , Rahamathulla Mohamed , Alshahrani Mohammad Y. , Alam Prawez , Shakeel Faiyaz
Published: October 2022

Cancer is one of the leading causes of morbidity and mortality around the globe and is likely to become the major cause of global death in the coming years. As per World Health Organization (WHO) report, every year there are over 10 and 9 million new cases and deaths from this disease. Chemotherapy, radiotherapy, and surgery are the three basic approaches to treating cancer. These approaches are aiming at eradicating all cancer cells with minimum off-target effects on other cell types. Most drugs have serious adverse effects due to the lack of target selectivity. On the other hand, resistance to already available drugs has emerged as a major obstacle in cancer chemotherapy, allowing cancer to proliferate irrespective of the chemotherapeutic agent. Consequently, it leads to multidrug resistance (MDR), a growing concern in the scientific community. To overcome this problem, in recent years, nanotechnology-based drug therapies have been explored and have shown great promise in overcoming resistance, with most nano-based drugs being explored at the clinical level. Through this review, we try to explain various mechanisms involved in multidrug resistance in cancer and the role nanotechnology has played in overcoming or reversing this resistance.
Comprehensive Review on Synthesis, Properties, and Applications of Phosphorus (PIII, PIV, PV) Substituted Acenes with More Than Two Fused Benzene Rings
Authors: Koprowski Marek , Owsianik Krzysztof , Knopik Łucja , Vivek Vivek , Romaniuk Adrian , Różycka-Sokołowska Ewa , Bałczewski Piotr
Published: October 2022

This comprehensive review, covering the years 1968–2022, is not only a retrospective investigation of a certain group of linearly fused aromatics, called acenes, but also a presentation of the current state of the knowledge on the synthesis, reactions, and applications of these compounds. Their characteristic feature is substitution of the aromatic system by one, two, or three organophosphorus groups, which determine their properties and applications. The (PIII, PIV, PV) phosphorus atom in organophosphorus groups is linked to the acene directly by a P-Csp2 bond or indirectly through an oxygen atom by a P-O-Csp2 bond.
Selenium: An Antioxidant with a Critical Role in Anti-Aging
Authors: Bjørklund Geir , Shanaida Mariia , Lysiuk Roman , Antonyak Halyna , Klishch Ivan , Shanaida Volodymyr , Peana Massimiliano
Published: October 2022

Aging is characterized by an imbalance between damage inflicted by reactive oxygen species (ROS) and the antioxidative defenses of the organism. As a significant nutritional factor, the trace element selenium (Se) may remodel gradual and spontaneous physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging. Se is involved in improving antioxidant defense, immune functions, and metabolic homeostasis. An inadequate Se status may reduce human life expectancy by accelerating the aging process or increasing vulnerability to various disorders, including immunity dysfunction, and cancer risk. This review highlights the available studies on the effective role of Se in aging mechanisms and shows the potential clinical implications related to its consumption. The main sources of organic Se and the advantages of its nanoformulations were also discussed.
Production of Minor Ginsenosides from Panax notoginseng Flowers by Cladosporium xylophilum
Authors: Li Yin-Fei , Liang Ying-Zhong , Cui Xiu-Ming , Shao Lin-Jiao , Lou Deng-Ji , Yang Xiao-Yan
Published: October 2022

Panax notoginseng flowers have the highest content of saponins compared to the other parts of Panax notoginseng, but minor ginsenosides have higher pharmacological activity than the main natural ginsenosides. Therefore, this study focused on the transformation of the main ginsenosides in Panax notoginseng flowers to minor ginsenosides using the fungus of Cladosporium xylophilum isolated from soil. The main ginsenosides Rb1, Rb2, Rb3, and Rc and the notoginsenoside Fa in Panax notoginseng flowers were transformed into the ginsenosides F2 and Rd2, the notoginsenosides Fd and Fe, and the ginsenoside R7; the conversion rates were 100, 100, 100, 88.5, and 100%, respectively. The transformation products were studied by TLC, HPLC, and MS analyses, and the biotransformation pathways of the major ginsenosides were proposed. In addition, the purified enzyme of the fungus was prepared with the molecular weight of 66.4 kDa. The transformation of the monomer ginsenosides by the crude enzyme is consistent with that by the fungus. Additionally, three saponins were isolated from the transformation products and identified as the ginsenoside Rd2 and the notoginsenosides Fe and Fd by NMR and MS analyses. This study provided a unique and powerful microbial strain for efficiently transformating major ginsenosides in P. notoginseng flowers to minor ginsenosides, which will help raise the functional and economic value of the P. notoginseng flower.
The Lebanese Red Algae Jania rubens: Promising Biomolecules against Colon Cancer Cells
Authors: Rifi Mariam , Radwan Zeina , AlMonla Reem , Fajloun Ziad , Sabatier Jean Marc , Kouzayha Achraf , El-Sabban Marwan , Mawlawi Hiba , Dassouki Zeina
Published: October 2022

Colorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their safety, effectiveness, and low cost. Jania rubens (J. rubens) is a red coral seaweed abundant in the Mediterranean and bears a significant pharmacological essence. Despite its therapeutic potential, the natural biomolecules extracted from this alga are poorly identified. In this study, the proximal analysis revealed high levels of total ash content (66%), 11.3% proteins, 14.5% carbohydrates, and only 4.5% lipids. The elemental identification showed magnesium and calcium were high among its macro minerals, (24 ± 0.5 mg/g) and (33 ± 0.5 mg/g), respectively. The Chlorophyll of J. rubens was dominated by other pigments with (0.82 ± 0.02 mg/g). A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay identified effective antioxidant activity in various J. rubens extracts. More importantly, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction and wound healing assays indicate that organic extracts from J. rubens significantly counteract the proliferation of colon cancer cell lines (HCT-116 and HT-29) and inhibit their migratory and metastatic properties in a dose and time-dependent manner. Overall, this study provides insight into the physicochemical properties of red seaweed, J. rubens, and identifies its significant antioxidant, cytotoxic, and anti-migratory potential on two colorectal cell lines, HCT-116 and HT-29.
A Novel Utilization of Water Extract of Suaeda Salsa in the Pd/C Catalyzed Suzuki–Miyaura Coupling Reaction
Authors: Ren Changyue , Zhang Hang , Chen Zhengjun , Gao Jie , Yang Mingyan , Yuan Zeli , Li Xinmin
Published: October 2022

Using biomass-derived solvents in various organic reactions is challenging for the fine chemicals industry. We herein report a Pd/C catalyzed Suzuki–Miyaura reaction in water extract of suaeda salsa (WES) without using external phosphine ligand, base, and organic solvent. The cross-coupling reactions were carried out in a basic WES medium with a broad substrate scope and wide functional group tolerance. Furthermore, the high purity of solid biaryl products can be obtained by column chromatography or filtration.
Effects of Fatty Alcohols with Different Chain Lengths on the Performance of Low pH Biomass-Based Foams for Radioactive Decontamination
Authors: Zhang Hao , Liang Lili , Xi Hailing , Liu Datong , Li Zhanguo , Lin Xiaoyan
Published: October 2022

Compared with polymers and nanoparticles, fatty alcohols can not only increase the stability of foam, but also maintain better foamability at pH < 2, which is beneficial to reduce waste liquid and increase decontamination efficiency for radioactive surface pollution. However, different fatty alcohols have different hydrophobic chain lengths. The effects of fatty alcohols with different chain lengths on the performance of decontamination foam were studied at pH < 2, to assist in the selection of suitable fatty alcohols as foam stabilizers. Combined with betaine surfactant and phytic acid, biomass-based foams were synthesized using fatty alcohols with different chain lengths. When the hydrophobic tail groups of the fatty alcohol and the surfactant were the same, the foam showed the best performance, including the lowest surface tension, the highest liquid film strength, the greatest sag-resistance and the best stability. However, when the hydrophobic tail groups were different, the space between adjacent surface active molecules was increased by thermal motion of the excess terminal tail segments (a tail-wagging effect), and the adsorption density reduced on the gas-liquid interface, leading to increased surface tension and decreased liquid film strength, sag-resistance and stability. The use of decontamination foam stabilized by fatty alcohols with the same hydrophobic group as the surfactant was found to increase the decontamination rate of radioactive uranium pollution from 64 to over 90% on a vertical surface.
Bioaccessibility of Phenolic Acids and Flavonoids from Buckwheat Biscuits Prepared from Flours Fermented by Lactic Acid Bacteria
Authors: Zieliński Henryk , Wiczkowski Wiesław , Topolska Joanna , Piskuła Mariusz Konrad , Wronkowska Małgorzata
Published: October 2022

The literature reports that the consumption of common buckwheat (Fagopyrum esculentum Moench), exactly the polyphenols it contains, is associated with a wide spectrum of health benefits. Therefore, the determination of the bioaccessibility of phenolic acids and flavonoids from buckwheat biscuits formulated from liquid-state fermented flours (BBF) by selected lactic acid bacteria (LAB) after gastrointestinal digestion was addressed in this study. Bioaccessibility could be defined as the fraction of a compound that is released from the food matrix in the gastrointestinal lumen and used for intestinal absorption. The bioaccessibility of eight phenolic acids (protocatechuic, vanillic, syringic ferulic, caffeic, sinapic, p-coumaric, and t-cinnamic) and six flavonoids (epicatechin, vitexin, orientin, apigenin, kaempferol, and luteolin) were provided for BBF and BBC (buckwheat biscuits prepared from fermented and unfermented flours, respectively). The bioaccessibility indexes (BI) indicated the high bioaccessibility of phenolic acids and improved bioaccessibility of flavonoids from BBF. Moreover, the data provide evidence for the suitability of selected LAB strains to be used as natural sour agents for further bakery product development rich in phenolic acids and flavonoids with LAB-dependent bioaccessibility.
Design, Synthesis and Biological Evaluation of Novel and Potent Protein Arginine Methyltransferases 5 Inhibitors for Cancer Therapy
Authors: Tang Yixuan , Huang Shihui , Chen Xingxing , Huang Junzhang , Lin Qianwen , Huang Lei , Wang Shuping , Zhu Qihua , Xu Yungen , Zou Yi
Published: October 2022

Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet need to discover novel and structurally diverse PRMT5 inhibitors with characterized therapeutic utility. Herein, a series of tetrahydroisoquinoline (THIQ) derivatives were designed and synthesized as PRMT5 inhibitors using GSK-3326595 as the lead compound. Among them, compound 20 (IC50: 4.2 nM) exhibits more potent PRMT5 inhibitory activity than GSK-3326595 (IC50: 9.2 nM). In addition, compound 20 shows high anti-proliferative effects on MV-4-11 and MDA-MB-468 tumor cells and low cytotoxicity on AML-12 hepatocytes. Furthermore, compound 20 possesses acceptable pharmacokinetic profiles and displays considerable in vivo antitumor efficacy in a MV-4-11 xenograft model. Taken together, compound 20 is an antitumor compound worthy of further study.
Antioxidant Effects of Bioactive Glasses (BGs) and Their Significance in Tissue Engineering Strategies
Authors: Kargozar Saeid , Hooshmand Sara , Hosseini Seyede Atefe , Gorgani Sara , Kermani Farzad , Baino Francesco
Published: October 2022

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.
Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo
Authors: Zhang Wang , Liu Xinjie , Sun Xun , Han Rongchun , Yu Nianjun , Liang Juan , Zhou An
Published: October 2022

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl4, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl4-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences.
Effect of 2-Methylthiazole Group on Photoinduced Birefringence of Thiazole-Azo Dye Host–Guest Systems at Different Wavelengths of Irradiation
Authors: Derkowska-Zielinska Beata , Kozanecka-Szmigiel Anna , Chomicki Dariusz , Smokal Vitaliy , Kawabe Yutaka , Krupka Oksana
Published: October 2022

The photoinduced birefringence behaviors of host–guest systems based on heterocyclic thiazole–azo dyes with different substituents, dispersed into PMMA matrix, were investigated under three excitation wavelengths, i.e., 405 nm, 445 nm or 532 nm. The wavelengths fell on the blue side, near the maximum or on the red side of the absorption bands of trans-azo dyes, respectively. We found that photoinduced birefringence was generated at a similar extent in all studied systems, except the system containing a 2-methyl-5-benzothiazolyl as thiazole–azo dye substituent. For this material, the achieved birefringence value was the highest among the whole series, regardless of the excitation wavelength. Moreover, we identified the optimal irradiation wavelength for efficient birefringence generation and showed that large absorption of excitation light by trans isomer does not account for achieving a significant degree of molecular alignment. The obtained results indicate that thiazole–azo dye with a 2-methyl-5-benzothiazolyl substituent shows promising photoinduced birefringence, and can be considered a dye potentially suitable for optical applications.
Comparing Variants of the Cell-Penetrating Peptide sC18 to Design Peptide-Drug Conjugates
Authors: Grabeck Joshua , Lützenburg Tamara , Frommelt Pia , Neundorf Ines
Published: October 2022

Herein, the design and synthesis of peptide-drug conjugates (PDCs) including different variants of the cell-penetrating peptide sC18 is presented. We first generated a series of novel sequence mutants of sC18 having either amino acid deletions and/or substitutions, and then tested their biological activity. The effects of histidine substituents were found to be not meaningful for sC18 uptake and cell selectivity. Moreover, building a nearly perfect amphipathic structure within a shortened sC18 derivative provided a peptide that was highly membrane-active, but also too cytotoxic. As a result, the most promising analog was sC18ΔE, which stands out due to its higher uptake efficacy compared to parent sC18. In the last set of experiments, we let the peptides react with the cytotoxic drug doxorubicin by Thiol–Michael addition to form novel PDCs. Our results indicate that sC18ΔE could be a more efficient drug carrier than parent sC18 for biomedical applications. However, cellular uptake using endocytosis and resulting entrapment of cargo inside vesicles is still a major critical step to overcome in CPP-containing peptide-drug development.
Antioxidants from Hyeronima macrocarpa Berries Loaded on Nanocellulose: Thermal and Antioxidant Stability
Authors: Alzate-Arbelaez Andrés Felipe , Cortés Farid B. , Rojano Benjamín A.
Published: October 2022

This study investigated the effect of different storage temperatures (35–55 °C) on the bioactive substances and antioxidant properties of Hyeronima macrocarpa berries loaded on nanocellulose. NC was extracted from banana pseudo-stems and presented an interesting surface and porosity properties. The acidified ethanol extract showed better anthocyanin extraction (1317 mg C3G eq./100 g FW) and was used for the preparation of the powdered product, which presented an intense and uniform magenta color, with CIELAB parameters of L* = 59.16, a* = 35.61, and b* = 7.08. The powder exhibited significant stability at storage temperatures of 35 and 45 °C, in which there was no significant loss of anthocyanins or a decrease in antioxidant capacity. In addition, the color was stable for up to 4 months without adding any preservative agent. The anthocyanin-rich extract of H. macrocarpa reached an estimated shelf-life of 315 days (stored at 35 °C), as a result of the impregnation process between the extract and NC, with the ability to protect the bioactives from degradation, due to NC surface properties.
Novel Strategy for Non-Aqueous Bioconjugation of Substituted Phenyl-1,2,4-triazole-3,5-dione Analogues
Authors: Hiscocks Hugh G. , Ung Alison T. , Pascali Giancarlo
Published: October 2022

A novel 4-[4-(pentafluoro-λ⁶-sulfanyl)phenyl]-1,2,4-triazole-3,5-dione (5a) was synthesised as a potential [18F]radio-prosthetic group for radiolabelling peptides and proteins via selective bioconjugation with the phenolic side chains of tyrosine residues. Preliminary conjugation tests revealed the rapid hydrolysis of 5a under semi-aqueous conditions; these results led to further investigation into the electronic substituent effects of PTAD derivatives and corresponding hydrolytic stabilities. Five derivatives of 5a with para substituents of varying electron donating and withdrawing effects were synthesised for the investigation. The bioconjugation of these derivatives with model tyrosine was monitored in both aqueous and organic media in the presence of a variety of catalysts. From these investigations, we have found HFIP to be an effective catalyst when used in tandem with DCM as a solvent to give PTAD-tyrosine conjugate products (6a–f) in satisfactory to good yields (54–79%), whereas analogous reactions performed in acetonitrile were unsuccessful. The discovery of this system has allowed for the successful conjugation of electron-deficient PTAD derivatives to tyrosine, which would otherwise be unachievable under aqueous reaction conditions. The inclusion of these electron-deficient, fluorinated PTAD derivatives for use in the PTAD-tyrosine conjugation will hopefully broaden their applicability within fields such as 19F-MRI and PET imaging.
Carduus edelbergii Rech. f. Mediated Fabrication of Gold Nanoparticles; Characterization and Evaluation of Antimicrobial, Antioxidant and Antidiabetic Potency of the Synthesized AuNPs
Authors: Jamil Shahid , Dastagir Ghulam , Foudah Ahmed Ibrahim , Alqarni Mohammed Hamed , Yusufoglu Hasan Soliman , Alkreathy Huda Mohammed , Ertürk Ömer , Shah Muhammad Abdur Rehman , Khan Rahmat Ali
Published: October 2022

Background: Due to the high expense, less effectiveness and more side effects of available synthetic medicine, the researchers and communities are focusing on phyto-based natural bioactive compounds, which are considered safer for the treatment of syndromes and chronic diseases. Aim: The current project was aimed to determine the phytochemicals constituents available in the aerial parts of methanol extract of Carduus edelbergii via GC-MS, fabrication of AuNPs mediated with the mentioned extract; characterization and evaluation of antimicrobial, antioxidant and antidiabetic potency of the synthesized AuNPs. Methods: Confirmation of green synthesis of AuNPs, functional groups responsible for the reduction in Au+, size and crystallinity, morphology and quantity of gold (Au) were carried out by Ultraviolet-Visible (UV-Vis) spectroscopy, Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and dispersive X-ray (EDX), respectively, whereas in vitro antioxidant characteristics were assessed by DPPH and ABTS assays. Wistar albino rats were used to test the anti-diabetic properties of the methanol extract and AuNPs. Results: GC-MS revealed that the diluted methanol extract of Carduus edelbergii consists of about 19 chemical constituents. Among the identified compounds, the 13-Docosenoic acid, methyl ester, (Z)—has the highest concentration (38.16%), followed by 9-Octadecenoic acid, methyl ester, (E)—(15.72%) and n-Hexadecanoic acid (15.07%). Methanol extract and its fabricated nanoparticles showed significant antioxidant and antimicrobial activities. In vivo antidiabetic study revealed a noteworthy (p < 0.05) decline in body weight and HDL and elevated concentration of blood glucose, bilirubin, creatinine, urea, triglyceride, VLDL, LDL, ALP, ALT and AST in diabetic control. The said changes were recovered significantly (p < 0.05) by treatment of diabetic rats with methanol extract (150 and 300 mg/Kg BW) and AuNPs of Carduus edelbergii (5 and 10 mg/Kg BW). Conclusion: The green synthesized AuNPs exhibit significant antioxidant, antimicrobial and antidiabetic characteristics.
Bio-Inspired Rhamnolipids, Cyclic Lipopeptides and a Chito-Oligosaccharide Confer Protection against Wheat Powdery Mildew and Inhibit Conidia Germination
Authors: Raouani Nour El Houda , Claverie Elodie , Randoux Béatrice , Chaveriat Ludovic , Yaseen Yazen , Yada Bopha , Martin Patrick , Cabrera Juan Carlos , Jacques Philippe , Reignault Philippe , Magnin-Robert Maryline , Lounès-Hadj Sahraoui Anissa
Published: October 2022

Plant protection is mainly based on the application of synthetic pesticides to limit yield losses resulting from diseases. However, the use of more eco-friendly strategies for sustainable plant protection has become a necessity that could contribute to controlling pathogens through a direct antimicrobial effect and/or an induction of plant resistance. Three different families of natural or bioinspired compounds originated from bacterial or fungal strains have been evaluated to protect wheat against powdery mildew, caused by the biotrophic Blumeria graminis f.sp. tritici (Bgt). Thus, three bio-inspired mono-rhamnolipids (smRLs), three cyclic lipopeptides (CLPs, mycosubtilin (M), fengycin (F), surfactin (S)) applied individually and in mixtures (M + F and M + F + S), as well as a chitosan oligosaccharide (COS) BioA187 were tested against Bgt, in planta and in vitro. Only the three smRLs (Rh-Eth-C12, Rh-Est-C12 and Rh-Succ-C12), the two CLP mixtures and the BioA187 led to a partial protection of wheat against Bgt. The higher inhibitor effects on the germination of Bgt spores in vitro were observed from smRLs Rh-Eth-C12 and Rh-Succ-C12, mycosubtilin and the two CLP mixtures. Taking together, these results revealed that such molecules could constitute promising tools for a more eco-friendly agriculture.
Identification and Quantification of Anthocyanin and Catechin Compounds in Purple Tea Leaves and Flakes
Authors: Abdel-Aal El-Sayed M. , Rabalski Iwona , Mats Lili , Rai Ishan
Published: October 2022

Tea is the first most popular beverage worldwide and is available in several selections such as black (fully oxidized), Oolong (partially oxidized) and green (non-oxidized), in addition to purple tea, an emerging variety derived from the same tea plant (Camellia sinensis). This study investigated purple tea leaves (non-oxidized) and flakes (water extractable) to thoroughly identify their composition of anthocyanins and catechins and to study the effect of a water extraction process on their compositional properties in comparison with green tea. Anthocyanin and catechin compounds were separated and quantified using UPLC, and their identity was confirmed using LC-MS/MS in positive and negative ionization modes. Delphinidin was the principal anthocyaninidin in purple tea, while cyanidin came in second. The major anthocyanin pigments in purple tea were delphinidin-coumaroyl-hexoside followed by delphinidin-3-galactoside and cyanidin-coumaroyl-hexoside. The water extraction process resulted in substantial reductions in anthocyanins in purple tea flakes. There were no anthocyanin compounds detected in green tea samples. Both purple and green tea types were rich in catechins, with green tea containing higher concentrations than purple tea. The main catechin in purple or green tea was epigallocatechin gallate (EGCG) followed by either epicatechin gallate (ECG) or epigallocatechin (EGC), subject to tea type. The extraction process increased the concentration of catechins in both purple and green tea flakes. The results suggest that purple tea holds promise in making healthy brews, natural colorants and antioxidants and/or functional ingredients for beverages, cosmetics and healthcare industries due to its high content of anthocyanins and catechins.
Effects of a Shift of the Signal Peptide Cleavage Site in Signal Peptide Variant on the Synthesis and Secretion of SARS-CoV-2 Spike Protein
Authors: Zhang Zhikai , Wan Xuan , Li Xinyue , Wan Chengsong
Published: October 2022

The COVID-19 pandemic is caused by SARS-CoV-2; the spike protein is a key structural protein that mediates infection of the host by SARS-CoV-2. In this study, we aimed to evaluate the effects of signal peptide on the secretion and release of SARS-CoV-2 spike protein. Therefore, we constructed a signal peptide deletion mutant and three signal peptide site-directed mutants. The (H) region and (C) region in the signal peptide of L5F-S13I mutant have changed significantly, compared with wild type, L5F and S13I. We demonstrated the effects of signal peptide on the secretion and synthesis of RBD protein, finding that mutation of S13 to I13 on the signal peptide is more conducive to the secretion of RBD protein, which was mainly due to the shift of the signal peptide cleavage site in the mutant S13I. Here, we not only investigated the structure of the N-terminal signal peptide of the SARS-CoV-2 spike protein but also considered possible secretory pathways. We suggest that the development of drugs that target the signal peptide of the SARS-CoV-2 spike protein may have potential to treat COVID-19 in the future.
Deactivatable Bisubstrate Inhibitors of Protein Kinases
Authors: Sõrmus Tanel , Lavogina Darja , Enkvist Erki , Uri Asko , Viht Kaido
Published: October 2022

Bivalent ligands, including bisubstrate inhibitors, are conjugates of pharmacophores, which simultaneously target two binding sites of the biomolecule. Such structures offer attainable means for the development of compounds whose ability to bind to the biological target could be modulated by an external trigger. In the present work, two deactivatable bisubstrate inhibitors of basophilic protein kinases (PKs) were constructed by conjugating the pharmacophores via linkers that could be cleaved in response to external stimuli. The inhibitor ARC-2121 incorporated a photocleavable nitrodibenzofuran-comprising β-amino acid residue in the structure of the linker. The pharmacophores of the other deactivatable inhibitor ARC-2194 were conjugated via reduction-cleavable disulfide bond. The disassembly of the inhibitors was monitored by HPLC-MS. The affinity and inhibitory potency of the inhibitors toward cAMP-dependent PK (PKAcα) were established by an equilibrium competitive displacement assay and enzyme activity assay, respectively. The deactivatable inhibitors possessed remarkably high 1–2-picomolar affinity toward PKAcα. Irradiation of ARC-2121 with 365 nm UV radiation led to reaction products possessing a 30-fold reduced affinity. The chemical reduction of ARC-2194 resulted in the decrease of affinity of over four orders of magnitude. The deactivatable inhibitors of PKs are valuable tools for the temporal inhibition or capture of these pharmacologically important enzymes.
Application of Biobased Solvents in Asymmetric Catalysis
Authors: Miele Margherita , Pillari Veronica , Pace Vittorio , Alcántara Andrés R. , de Gonzalo Gonzalo
Published: October 2022

The necessity of more sustainable conditions that follow the twelve principles of Green Chemistry have pushed researchers to the development of novel reagents, catalysts and solvents for greener asymmetric methodologies. Solvents are in general a fundamental part for developing organic processes, as well as for the separation and purification of the reaction products. By this reason, in the last years, the application of the so-called green solvents has emerged as a useful alternative to the classical organic solvents. These solvents must present some properties, such as a low vapor pressure and toxicity, high boiling point and biodegradability, and must be obtained from renewable sources. In the present revision, the recent application of these biobased solvents in the synthesis of optically active compounds employing different catalytic methodologies, including biocatalysis, organocatalysis and metal catalysis, will be analyzed to provide a novel tool for carrying out more ecofriendly organic processes.
Formation and Analysis of Volatile and Odor Compounds in Meat—A Review
Authors: Bleicher Julian , Ebner Elmar E. , Bak Kathrine H.
Published: October 2022

The volatile composition and odor of meat and meat products is based on the precursors present in the raw meat. These are influenced by various pre-slaughter factors (species, breed, sex, age, feed, muscle type). Furthermore, post-mortem conditions (chiller aging, cooking conditions, curing, fermentation, etc.) determine the development of meat volatile organic compounds (VOCs). In this review, the main reactions leading to the development of meat VOCs such as the Maillard reaction; Strecker degradation; lipid oxidation; and thiamine, carbohydrate, and nucleotide degradation are described. The important pre-slaughter factors and post-mortem conditions influencing meat VOCs are discussed. Finally, the pros, cons, and future perspectives of the most commonly used sample preparation techniques (solid-phase microextraction, stir bar sorptive extraction, dynamic headspace extraction) and analytical methods (gas chromatography mass spectrometry and olfactometry, as well as electronic noses) for the analysis of meat VOCs are discussed, and the continued importance of sensorial analysis is pinpointed.
Design and Synthesis of Coumarin Derivatives as Cytotoxic Agents through PI3K/AKT Signaling Pathway Inhibition in HL60 and HepG2 Cancer Cells
Authors: Kishk Safaa M. , Eltamany Enas E. , Nafie Mohamed S. , Khinkar Roaa M. , Hareeri Rawan H. , Elhady Sameh S. , Yassen Asmaa S. A.
Published: October 2022

In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (4) had a significant cytotoxic effect against HL60 cells (IC50 = 8.09 µM), while compound (8b) had a noticeable activity against HepG2 cells (IC50 = 13.14 µM). Compounds (4) and (8b) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.
Anti-Mycobacterial Activity of Flavonoid and Pyrimidine Compounds
Authors: Garg Saurabh , Kumar Rakesh , Kunimoto Dennis , Rayat Gina R.
Published: October 2022

We evaluated the anti-mycobacterial effect of a flavonoid 5,7-dihydroxy-2-(4-hydroxyphenyl) 4H-chromen-4-one (1) and two pyrimidines, 4-hydroxy-2-dimethylamino-5-nitroso-6-aminopyrimidine (2) and 2-chloro-5-n-nonylpyrimidine (3) in vitro against Mycobacterium tuberculosis (M. tuberculosis, H37Ra) and Mycobacterium avium (M. avium), using a Microplate Alamar Blue Assay (MABA). The effects of the compounds 1–3 in combination with first- and second-line anti-TB drugs isoniazid, rifampicin, cycloserine, and clarithromycin on the growth of M. tuberculosis and M. avium were also evaluated in in vitro assays. As a single agent, compounds 1 and 2 exhibited modest activity while compound 3 was the most effective against M. tuberculosis and M. avium. When compounds 1–3 were evaluated at lower than 50% of their inhibitory concentrations in a two-drug combination with isoniazid or rifampicin, they showed additive to synergistic interactions. This inhibitory effect was improved when each of the three compounds was tested together in a three-drug combination with two of the first-line anti-TB drugs. Compounds 1–3 also demonstrated strong synergistic interaction in combination with cycloserine and clarithromycin in inhibiting the growth of M. tuberculosis and M. avium, respectively. This study demonstrated that compounds 1–3 have potential to be developed as effective anti-TB agents with combined use.
Indane Based Molecular Motors: UV-Switching Increases Number of Isomers
Authors: Shendrikov Valeriy P. , Alekseeva Anna S. , Kot Erik F. , Mineev Konstantin S. , Tretiakova Daria S. , Ece Abdulilah , Boldyrev Ivan A.
Published: October 2022

We describe azophenylindane based molecular motors (aphin-switches) which have two different rotamers of trans-configuration and four different rotamers of cis-configuration. The behaviors of these motors were investigated both experimentally and computationally. The conversion of aphin-switch does not yield single isomer but a mixture of these. Although the trans to cis conversion leads to the increase of the system entropy some of the cis-rotamers can directly convert to each other while others should convert via trans-configuration. The motion of aphin-switches resembles the work of a mixing machine with indane group serving as a base and phenol group serving as a beater. The aphin-switches presented herein may provide a basis for promising applications in advanced biological systems or particularly in cases where on demand disordering of molecular packing has value, such as lipid bilayers.
“Smart Extraction Chain” with Green Solvents: Extraction of Bioactive Compounds from Picea abies Bark Waste for Pharmaceutical, Nutraceutical and Cosmetic Uses
Authors: Sut Stefania , Maccari Erica , Zengin Gokhan , Ferrarese Irene , Loschi Francesca , Faggian Marta , Paolo Bertoni , De Zordi Nicola , Dall’Acqua Stefano
Published: October 2022

Secondary metabolites from the sawmill waste Picea abies bark were extracted using an innovative two-step extraction that includes a first step with supercritical CO2 (SCO2) and a second step using green solvents, namely ethanol, water, and water ethanol mixture. Maceration (M), ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE) techniques were applied in the second step. A total of nineteen extract were obtained and yield were compared. Bark extracts were characterized by LC-DAD-MSn and classes of compounds were quantified as abietane derivatives, piceasides, flavonoids, and phenolics to compare different extractions. Obtained extracts were studied by in vitro assay to evaluate potential pharmaceutical, nutraceutical and cosmetic uses assessing the antioxidant activity as well as the inhibitory activity on target enzymes. Results show that the “smart extraction chain” is advantageous in term of yield of extraction and phytoconstituent concentration. SCO2 extract, presenting a unique composition with a large amount of abietane derivatives, exerted the best activity for amylase inhibition compared to the other extracts.
Comprehensive Lichenometabolomic Exploration of Ramalina conduplicans Vain Using UPLC-Q-ToF-MS/MS: An Identification of Free Radical Scavenging and Anti-Hyperglycemic Constituents
Authors: Kumar Tatapudi Kiran , Siva Bandi , Anand Ajay , Anusha Komati , Mohabe Satish , Reddy Araveeti Madhusudana , Le Devehat Françoise , Tiwari Ashok Kumar , Boustie Joël , Babu Katragadda Suresh
Published: October 2022

In this study, we propose ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-QToF-MS/MS)-guided metabolite isolation as a choice analytical approach to the ongoing structure–activity investigations of chemical isolates from the edible lichen, Ramalina conduplicans Vain. This strategy led to the isolation and identification of a new depside (5) along with 13 known compounds (1–4, 6–14), most of which being newly described in this lichen species. The structures of the isolates were established by detailed analysis of their spectral data (IR, NMR, and Mass). The acetone extract was further analyzed by UPLC-Q-ToF-MS/MS in a negative ionization mode, which facilitated the identification and confirmation of 18 compounds based on their fragmentation patterns. The antioxidant capacities of the lichen acetone extract (AE) and isolates were measured by tracking DPPH and ABTS free radical scavenging activities. Most isolates displayed marked radical scavenging activities against ABTS while moderate activities were observed against DPPH radical scavenging. Except for atranol (14), oxidative DNA damage was limited by all the tested compounds, with a marked protection for the novel isolated compound (5), as previously noted for the acetone extract (p < 0.001). Furthermore, compound (4) and acetone extract (AE) have inhibited intestinal α-glucosidase enzyme significantly (p < 0.01). Although some phytochemical studies were already performed on this lichen, this study provided new insights into the isolation and identification of bioactive compounds, illustrating interest in future novel analytical techniques.
AVA-NP-695 Selectively Inhibits ENPP1 to Activate STING Pathway and Abrogate Tumor Metastasis in 4T1 Breast Cancer Syngeneic Mouse Model
Authors: Goswami Avijit , Deb Barnali , Goyal Sandeep , Gosavi Abhishek , Mali Mukund , Martis Ashwita M. , Khurana Princy , Gangar Mukesh , Raykar Digambar , Mohanty Ankita , Kulkarni Aditya
Published: October 2022

Cyclic GMP-AMP synthase (cGAS) is an endogenous DNA sensor that synthesizes cyclic guanosine monophosphate–adenosine monophosphate (2′3′-cGAMP) from ATP and GTP. 2′3′-cGAMP activates the stimulator of interferon genes (STING) pathway, resulting in the production of interferons and pro-inflammatory cytokines. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the phosphodiesterase that negatively regulates the STING pathway by hydrolyzing 2′3′-cGAMP. It has been established that the cGAS–STING pathway plays a major role in inhibiting tumor growth by upregulating T cell response. Herein, we demonstrate that AVA-NP-695, a selective and highly potent ENPP1 inhibitor, apart from the immunomodulatory effect also modulates cancer metastasis by negatively regulating epithelial–mesenchymal transition (EMT). We established that the combined addition of 2′3′-cGAMP and AVA-NP-695 significantly abrogated the transforming growth factor beta (TGF-ꞵ)-induced EMT in MDA-MB-231 cells. Finally, results from the in vivo study showed superior tumor growth inhibition and impact on tumor metastasis of AVA-NP-695 compared to Olaparib and PD-1 in a syngeneic 4T1 breast cancer mouse model. The translation of efficacy from in vitro to in vivo 4T1 tumor model provides a strong rationale for the therapeutic potential of AVA-NP-695 against triple-negative breast cancer (TNBC) as an immunomodulatory and anti-metastatic agent.
Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation
Authors: Ezzat Shahira M. , Teba Heba El Sayed , Shahin Inas G. , Hafez Ahmed M. , Kamal Aliaa M. , Aborehab Nora M.
Published: October 2022

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.
Correction: Qian et al. Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways. Molecules 2016, 21, 1406
Authors: Qian Kaiyu , Wang Gang , Cao Rui , Liu Tao , Qian Guofeng , Guan Xinyuan , Guo Zhongqiang , Xiao Yu , Wang Xinghuan
Published: October 2022

During the course of a review of our publications, an inadvertent error in the article [...]
Hierarchically Annular Mesoporous Carbon Derived from Phenolic Resin for Efficient Removal of Antibiotics in Wastewater
Authors: Lin Xuexia , Su Mengxing , Fang Feixiang , Hong Jiafu , Zhang Yumeng , Zhou Shu-Feng
Published: October 2022

Antibiotics have become a new type of environmental pollutant due to their extensive use. High-performance adsorbents are of paramount significance for a cost-effective and environmentally friendly strategy to remove antibiotics from water environments. Herein, we report a novel annular mesoporous carbon (MCN), prepared by phenolic resin and triblock copolymer F127, as a high-performance adsorbent to remove penicillin, streptomycin, and tetracycline hydrochloride from wastewater. The MCNs have high purity, rich annular mesoporosity, a high surface area (605.53 m2/g), and large pore volume (0.58 cm3/g), improving the adsorption capacity and facilitating the efficient removal of penicillin, streptomycin, and tetracycline hydrochloride from water. In the application of MCNs to treat these three kinds of residual antibiotics, the adsorption amounts of tetracycline hydrochloride were higher than penicillin and streptomycin, and the adsorption capacity was up to 880.6 mg/g. Moreover, high removal efficiency (99.6%) and excellent recyclability were achieved. The results demonstrate that MCN adsorbents have significant potential in the treatment of water contaminated with antibiotics.
Cellulose Nanofibers from Schinus molle: Preparation and Characterization
Authors: Razzak Abir , Khiari Ramzi , Moussaoui Younes , Belgacem Mohamed Naceur
Published: October 2022

Schinus molle (SM) was investigated as a primary source of cellulose with the aim of discovering resources to generate cellulose nanofibers (CNF). The SM was put through a soda pulping process to purify the cellulose, and then, the fiber was treated with an enzymatic treatment. Then, a twin-screw extruder and/or masuko were utilized to help with fiber delamination during the nanofibrillation process. After the enzymatic treatment, the twin-screw extruder and masuko treatment give a yield of 49.6 and 50.2%, respectively. The optical and atomic force microscopy, morfi, and polymerization degrees of prepared cellulosic materials were established. The pulp fibers, collected following each treatment stage, demonstrated that fiber characteristics such as length and crystallinity varied according to the used treatment (mechanical or enzymatic treatment). Obviously, the enzymic treatment resulted in shorter fibers and an increased degree of polymerization. However, the CNF obtained after enzymatic and extrusion treatment was achieved, and it gave 19 nm as the arithmetic width and a Young’s modulus of 8.63 GPa.