cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.23899844.v1
title: Bioassay-guided isolation and <i>in silico</i> study of antihyperlipidemic compounds from <i>Onosma hispidum</i> Wall

description: Isolation of bioactive compounds from plants and their therapeutic evaluation is crucial in the pursuit of novel phytochemicals and contributes an indispensable role in drug discovery and design. The literature has documented the hypolipidemic effect of numerous <i>Onosma</i> species. Taking that into consideration, the current study was designed to isolate, purify and evaluate the antihyperlipidemic potential of leaves of <i>Onosma hispidum</i> Wall. For the first time, the bioassay-guided isolation led to the separation of 3 compounds that were identified by spectroscopic techniques as o-phthalic acid bis-(2-ethyl decyl)-ester (1), bis (2-ethyloctyl) phthalate (2), and 1,2 benzenedicarboxylic acid bis(2-methyl heptyl) ester (3). Lipase inhibition assay was utilized to scrutinize the antihyperlipidemic potential of methanolic extract fractions and subsequently isolated compounds. Further, the isolated compounds were employed for <i>in silico</i> studies <i>via</i> molecular docking, molecular mechanics with generalized born and surface area solvation (MM-GBSA), and MD simulations with Pancreatic Lipase Colipase (PDB ID: 1LPB). Molecular docking and MM-GBSA of isolated compounds were employed to explain the mode of binding between the protein–ligand complex and binding free energy calculation, respectively. Since compound (3) displayed the best docking score of −6.689 kcal/mol as compared to orlistat −5.529 kcal/mol with PDB: 1LPB. So, it was chosen for MD simulations to evaluate ligand stability and flexibility of the complex which was validated by the fluctuation of α-carbon chain, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and type of interactions involved which authenticated the <i>in vitro</i> lipase inhibitory potential. Overall, <i>in silico</i> and <i>in vitro</i> results validated that compound (3) could be exploited as a promising pancreatic lipase inhibitor. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23936813
title: Molecular modeling strategy for detailing the primary mechanism of action of copanlisib to PI3K: combined ligand-based and target-based approach

description: Since dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with the pathogenesis of cancer, inflammation, and autoimmunity, PI3K has emerged as an attractive target for drug development. Although copanlisib is the first pan-PI3K inhibitor to be approved for clinical use, the precise mechanism by which it acts on PI3K has not been fully elucidated. To reveal the binding mechanisms and structure-activity relationship between PI3K and copanlisib, a comprehensive modeling approach that combines 3D-quantitative structure-activity relationship (3D-QSAR), pharmacophore model, and molecular dynamics (MD) simulation was utilized. Initially, the structure-activity relationship of copanlisib and its derivatives were explored by constructing a 3D-QSAR. Then, the key chemical characteristics were identified by building common feature pharmacophore models. Finally, MD simulations were performed to elucidate the important interactions between copanlisib and different PI3K subtypes, and highlight the key residues for tight-binding inhibitors. The present study uncovered the principal mechanism of copanlisib’s action on PI3K at the theoretical level, and these findings might provide guidance for the rational design of pan-PI3K inhibitors. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23936813.v1
title: Molecular modeling strategy for detailing the primary mechanism of action of copanlisib to PI3K: combined ligand-based and target-based approach

description: Since dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is associated with the pathogenesis of cancer, inflammation, and autoimmunity, PI3K has emerged as an attractive target for drug development. Although copanlisib is the first pan-PI3K inhibitor to be approved for clinical use, the precise mechanism by which it acts on PI3K has not been fully elucidated. To reveal the binding mechanisms and structure-activity relationship between PI3K and copanlisib, a comprehensive modeling approach that combines 3D-quantitative structure-activity relationship (3D-QSAR), pharmacophore model, and molecular dynamics (MD) simulation was utilized. Initially, the structure-activity relationship of copanlisib and its derivatives were explored by constructing a 3D-QSAR. Then, the key chemical characteristics were identified by building common feature pharmacophore models. Finally, MD simulations were performed to elucidate the important interactions between copanlisib and different PI3K subtypes, and highlight the key residues for tight-binding inhibitors. The present study uncovered the principal mechanism of copanlisib’s action on PI3K at the theoretical level, and these findings might provide guidance for the rational design of pan-PI3K inhibitors. Communicated by Ramaswamy H. Sarma
DOI: 10.15468/dl.9wz4c5
title: Occurrence Download

description: A dataset containing 445 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Country is Chile",
 "TaxonKey is Galictis cuja"
 ]
}

 The dataset includes 445 records from 14 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0039677-251120083545085/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.23815303
title: Identification of potential inhibitors of <i>Mtb</i> InhA: a pharmacoinformatics approach

description: The emergence of superbugs of multi-drug resistant (MDR/RR) and extensively drug-resistant (XDR) <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strains at a faster rate is posing a serious threat to Tuberculosis (TB) control worldwide. <i>Mtb</i> enoyl-acyl carrier protein reductase (InhA) is a well-established target of the front-line anti-TB prodrug Isoniazid (INH), which requires activation by Catalase-peroxidase enzyme (KatG) in order to inhibit InhA enzyme, that is crucial for the biosynthesis of the mycobacterial cell wall. Currently, due to widespread resistance to this drug, it is necessary to identify new clinical candidates that directly inhibit InhA enzyme and do not require activation by KatG, thereby circumventing most of the resistance mechanisms. In the present study, high-throughput virtual screening of ASINEX database was carried out to identify potential direct inhibitors of <i>Mtb</i> InhA. Best twenty compounds with good binding energies ranging between −12.36 and −9.27 kcal/mol were selected as promising virtual screening hits. These molecules were subjected to ADME study followed by toxicity prediction. Finally, four top-ranked molecules which are structurally diverse and possess best binding affinity than the co-crystalized ligand have been chosen for MD simulation studies followed by MM-GBSA analysis to validate and ensure the stability of hits in the active site of the enzyme. Based on the 100 ns MD simulation studies and binding free energy estimates, three hit molecules B244, B369, and B310 could be considered as potential inhibitors for <i>Mtb</i> InhA, which are likely to be potent against INH-resistant <i>Mtb</i> strains after successful experimental validation. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23815303.v1
title: Identification of potential inhibitors of <i>Mtb</i> InhA: a pharmacoinformatics approach

description: The emergence of superbugs of multi-drug resistant (MDR/RR) and extensively drug-resistant (XDR) <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strains at a faster rate is posing a serious threat to Tuberculosis (TB) control worldwide. <i>Mtb</i> enoyl-acyl carrier protein reductase (InhA) is a well-established target of the front-line anti-TB prodrug Isoniazid (INH), which requires activation by Catalase-peroxidase enzyme (KatG) in order to inhibit InhA enzyme, that is crucial for the biosynthesis of the mycobacterial cell wall. Currently, due to widespread resistance to this drug, it is necessary to identify new clinical candidates that directly inhibit InhA enzyme and do not require activation by KatG, thereby circumventing most of the resistance mechanisms. In the present study, high-throughput virtual screening of ASINEX database was carried out to identify potential direct inhibitors of <i>Mtb</i> InhA. Best twenty compounds with good binding energies ranging between −12.36 and −9.27 kcal/mol were selected as promising virtual screening hits. These molecules were subjected to ADME study followed by toxicity prediction. Finally, four top-ranked molecules which are structurally diverse and possess best binding affinity than the co-crystalized ligand have been chosen for MD simulation studies followed by MM-GBSA analysis to validate and ensure the stability of hits in the active site of the enzyme. Based on the 100 ns MD simulation studies and binding free energy estimates, three hit molecules B244, B369, and B310 could be considered as potential inhibitors for <i>Mtb</i> InhA, which are likely to be potent against INH-resistant <i>Mtb</i> strains after successful experimental validation. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23925913
title: <i>In Vitro</i> and <i>in silico</i> studies to explore potent antidiabetic inhibitor against human pancreatic alpha-amylase from the methanolic extract of the green microalga <i>Chlorella vulgaris</i>

description: Today’s era and lifestyle have led to a quick rise in cases of diabetes. Diabetes mellitus (DM) has risen to the top of the list of serious diseases and stems from different health disorders. Human pancreatic alpha-amylase (HPA) enzyme plays a critical role in the digestion of carbohydrates, and inhibitors of alpha-amylase have been investigated as a way to slow the absorption of carbohydrates and reduce postprandial (after meal) hyperglycemia in patients with diabetes. Recently algal derivatives have been studied for their potential as a new drug against diabetes and other diseases. The study is aimed to find active biochemical compounds from the methanolic extract of <i>Chlorella vulgaris</i>. The <i>in vitro</i> studies were carried out and the results revealed that methanolic extract from <i>C. vulgaris</i> showed abundant inhibition efficacy of the α-amylase (IC<sub>50</sub> of about 2.66 µg/mL) compared to acarbose (IC<sub>50</sub> of about 2.85 µg/mL), a standard, commercial inhibitor. All the bioactive compounds from the methanolic extract were identified from the GCMS study and considered for <i>in silico</i> evaluation. Out of 14 bioactive compounds from GCMS, compound C3 showed higher docking energy (-8.3 kcal/mol) compared to other compounds. Subsequently, the comparative molecular dynamic simulation of apo and ligand-bound (compound C3 and acarbose) α-amylase complexes showed overall structural stability for compound C3 at the active site of α-amylase from various MD analyses. Hence, we believe, the bioactive compounds identified from GCMS may assist in diabetic therapeutics. Moreover, the compound C3 identified in this study could be a potential antidiabetic therapeutic inhibitor. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23925913.v1
title: <i>In Vitro</i> and <i>in silico</i> studies to explore potent antidiabetic inhibitor against human pancreatic alpha-amylase from the methanolic extract of the green microalga <i>Chlorella vulgaris</i>

description: Today’s era and lifestyle have led to a quick rise in cases of diabetes. Diabetes mellitus (DM) has risen to the top of the list of serious diseases and stems from different health disorders. Human pancreatic alpha-amylase (HPA) enzyme plays a critical role in the digestion of carbohydrates, and inhibitors of alpha-amylase have been investigated as a way to slow the absorption of carbohydrates and reduce postprandial (after meal) hyperglycemia in patients with diabetes. Recently algal derivatives have been studied for their potential as a new drug against diabetes and other diseases. The study is aimed to find active biochemical compounds from the methanolic extract of <i>Chlorella vulgaris</i>. The <i>in vitro</i> studies were carried out and the results revealed that methanolic extract from <i>C. vulgaris</i> showed abundant inhibition efficacy of the α-amylase (IC<sub>50</sub> of about 2.66 µg/mL) compared to acarbose (IC<sub>50</sub> of about 2.85 µg/mL), a standard, commercial inhibitor. All the bioactive compounds from the methanolic extract were identified from the GCMS study and considered for <i>in silico</i> evaluation. Out of 14 bioactive compounds from GCMS, compound C3 showed higher docking energy (-8.3 kcal/mol) compared to other compounds. Subsequently, the comparative molecular dynamic simulation of apo and ligand-bound (compound C3 and acarbose) α-amylase complexes showed overall structural stability for compound C3 at the active site of α-amylase from various MD analyses. Hence, we believe, the bioactive compounds identified from GCMS may assist in diabetic therapeutics. Moreover, the compound C3 identified in this study could be a potential antidiabetic therapeutic inhibitor. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23909523
title: Computational peptide engineering approach for selection of the new C05 antibody-driven peptide with potency to blocking influenza a virus attachment; from <i>in silico</i> to <i>in vivo</i>

description: Antiviral drugs are currently used to prevent or treat viral infections like influenza A Virus (IAV). Nonetheless, annual genetic mutations of influenza viruses make them resistant to efficient treatment by current medications. Antiviral peptides have recently attracted researchers’ attention and can potentially supplant the current medications. This study aimed to design peptides against IAV propagation. For this purpose, P2 and P3 peptides were computationally designed based on the HCDR3 region of the C05 antibody (a monoclonal antibody that neutralizes influenza HA protein and inhibits the virus attachment). The synthesized peptides were tested against the influenza A virus (A/Puerto Rico/8/34 (H1N1)) <i>in vitro</i>, and the most efficient peptide was selected for <i>in vivo</i> experiments. It was shown that the designed peptide shows much more prophylactic and therapeutic effects against the virus. These findings demonstrated that the designed peptide can control the virus infection without any cytotoxicity effect. Antiviral peptide design is acknowledged as a critical tactic to manage viral infections by preventing viral binding to the host cells. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23909523.v1
title: Computational peptide engineering approach for selection of the new C05 antibody-driven peptide with potency to blocking influenza a virus attachment; from <i>in silico</i> to <i>in vivo</i>

description: Antiviral drugs are currently used to prevent or treat viral infections like influenza A Virus (IAV). Nonetheless, annual genetic mutations of influenza viruses make them resistant to efficient treatment by current medications. Antiviral peptides have recently attracted researchers’ attention and can potentially supplant the current medications. This study aimed to design peptides against IAV propagation. For this purpose, P2 and P3 peptides were computationally designed based on the HCDR3 region of the C05 antibody (a monoclonal antibody that neutralizes influenza HA protein and inhibits the virus attachment). The synthesized peptides were tested against the influenza A virus (A/Puerto Rico/8/34 (H1N1)) <i>in vitro</i>, and the most efficient peptide was selected for <i>in vivo</i> experiments. It was shown that the designed peptide shows much more prophylactic and therapeutic effects against the virus. These findings demonstrated that the designed peptide can control the virus infection without any cytotoxicity effect. Antiviral peptide design is acknowledged as a critical tactic to manage viral infections by preventing viral binding to the host cells. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23943160
title: Computational insights into the role of structurally diverse plant secondary metabolites as inhibitors against Imidazole Glycerol Phosphate Dehydratase of <i>Mycobacterium tuberculosis</i>

description: <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is one of the major causes of death worldwide and there is a pressing need for the development of novel drug leads. The Imidazole Glycerol Phosphate Dehydratase (IGPD) of <i>Mtb</i> is one of the key enzymes in the histidine biosynthesis pathway and has been recognized as the potentially underexploited drug target for anti-tuberculosis treatment. In the present study, 6063 structurally diverse plant secondary metabolites (PSM) were screened for their efficiency in inhibiting the catalytic activity of IGPD through molecular docking. The top 150 PSMs with the lowest binding energy represent the chemical classes, including Tannins (34%), Flavonoid Glycosides (14%), Terpene Glycosides (10%), Steroid Lactones (9.3%), Flavonoids (6.6%), Steroidal Glycosides (4.6%), etc. Bismahanine, Ashwagandhanolide, and Daurisoline form stable IGPD-inhibitor complexes with binding free energies of −291.3 ± 16.5, −279.0 ± 25.0, and −279.8 ± 17.6 KJ/mol, respectively, as determined by molecular dynamics simulations. These PSM demonstrated strong H-bond interactions with the amino acid residues Ile279, Arg281, and Lys276 in the catalytic region of IGPD, as revealed by structural snapshots. On the basis of our findings, these three PSM could be considered as possible leads against IGPD and should be explored <i>in vitro</i> and <i>in vivo</i>. Communicated by Ramaswamy H. Sarma Imidazole Glycerol Phosphate Dehydratase (IGPD) is an unexplored drug target in tuberculosis therapy. Inhibitory potential of 6063 plant secondary metabolites (PSM) against IGPD enzyme was studied. Ensemble docking and structural-activity relationship studies ascertained the group of diverse molecules. MD simulations predicted Bismahanine and Ashwagandhanolide as possible inhibitors of IGPD.
DOI: 10.6084/m9.figshare.23943160.v1
title: Computational insights into the role of structurally diverse plant secondary metabolites as inhibitors against Imidazole Glycerol Phosphate Dehydratase of <i>Mycobacterium tuberculosis</i>

description: <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is one of the major causes of death worldwide and there is a pressing need for the development of novel drug leads. The Imidazole Glycerol Phosphate Dehydratase (IGPD) of <i>Mtb</i> is one of the key enzymes in the histidine biosynthesis pathway and has been recognized as the potentially underexploited drug target for anti-tuberculosis treatment. In the present study, 6063 structurally diverse plant secondary metabolites (PSM) were screened for their efficiency in inhibiting the catalytic activity of IGPD through molecular docking. The top 150 PSMs with the lowest binding energy represent the chemical classes, including Tannins (34%), Flavonoid Glycosides (14%), Terpene Glycosides (10%), Steroid Lactones (9.3%), Flavonoids (6.6%), Steroidal Glycosides (4.6%), etc. Bismahanine, Ashwagandhanolide, and Daurisoline form stable IGPD-inhibitor complexes with binding free energies of −291.3 ± 16.5, −279.0 ± 25.0, and −279.8 ± 17.6 KJ/mol, respectively, as determined by molecular dynamics simulations. These PSM demonstrated strong H-bond interactions with the amino acid residues Ile279, Arg281, and Lys276 in the catalytic region of IGPD, as revealed by structural snapshots. On the basis of our findings, these three PSM could be considered as possible leads against IGPD and should be explored <i>in vitro</i> and <i>in vivo</i>. Communicated by Ramaswamy H. Sarma Imidazole Glycerol Phosphate Dehydratase (IGPD) is an unexplored drug target in tuberculosis therapy. Inhibitory potential of 6063 plant secondary metabolites (PSM) against IGPD enzyme was studied. Ensemble docking and structural-activity relationship studies ascertained the group of diverse molecules. MD simulations predicted Bismahanine and Ashwagandhanolide as possible inhibitors of IGPD.
DOI: 10.34740/kaggle/dsv/14068214
title: Peer-to-Peer Boliviano (BOB) Exchange Data
DOI: 10.6084/m9.figshare.23815761
title: Identification of candidate target genes of oral squamous cell carcinoma using high-throughput RNA-Seq data and <i>in silico</i> studies of their interaction with naturally occurring bioactive compounds

description: Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of all kinds of oral neoplasms that develop in the oral cavity. It is a type of malignancy that shows high morbidity and recurrence rate, but data on the disease’s target genes and biomarkers is still insufficient. In this study, <i>in silico</i> studies have been performed to find out the novel target genes and their potential therapeutic inhibitors for the effective and efficient treatment of OSCC. The DESeq2 package of RStudio was used in the current investigation to screen and identify differentially expressed genes for OSCC. As a result of gene expression analysis, the top 10 novel genes were identified using the Cytohubba plugin of Cytoscape, and among them, the ubiquitin-conjugating enzyme (UBE2D1) was found to be upregulated and playing a significant role in the progression of human oral cancers. Following this, naturally occurring compounds were virtually evaluated and simulated against the discovered novel target as prospective drugs utilizing the Maestro, Schrodinger, and Gromacs software. In a simulated screening of naturally occurring potential inhibitors against the novel target UBE2D1, Epigallocatechin 3-gallate, Quercetin, Luteoline, Curcumin, and Baicalein were identified as potent inhibitors. Novel identified gene UBE2D1 has a significant role in the proliferation of human cancers through suppression of ‘guardian of genome’ p53 <i>via</i> ubiquitination dependent pathway. Therefore, the treatment of OSCC may benefit significantly from targeting this gene and its discovered naturally occurring inhibitors. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.23815761.v2
title: Identification of candidate target genes of oral squamous cell carcinoma using high-throughput RNA-Seq data and <i>in silico</i> studies of their interaction with naturally occurring bioactive compounds

description: Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of all kinds of oral neoplasms that develop in the oral cavity. It is a type of malignancy that shows high morbidity and recurrence rate, but data on the disease’s target genes and biomarkers is still insufficient. In this study, <i>in silico</i> studies have been performed to find out the novel target genes and their potential therapeutic inhibitors for the effective and efficient treatment of OSCC. The DESeq2 package of RStudio was used in the current investigation to screen and identify differentially expressed genes for OSCC. As a result of gene expression analysis, the top 10 novel genes were identified using the Cytohubba plugin of Cytoscape, and among them, the ubiquitin-conjugating enzyme (UBE2D1) was found to be upregulated and playing a significant role in the progression of human oral cancers. Following this, naturally occurring compounds were virtually evaluated and simulated against the discovered novel target as prospective drugs utilizing the Maestro, Schrodinger, and Gromacs software. In a simulated screening of naturally occurring potential inhibitors against the novel target UBE2D1, Epigallocatechin 3-gallate, Quercetin, Luteoline, Curcumin, and Baicalein were identified as potent inhibitors. Novel identified gene UBE2D1 has a significant role in the proliferation of human cancers through suppression of ‘guardian of genome’ p53 <i>via</i> ubiquitination dependent pathway. Therefore, the treatment of OSCC may benefit significantly from targeting this gene and its discovered naturally occurring inhibitors. Communicated by Ramaswamy H. Sarma