cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24465493.v1
title: The cytotoxic potential of sinapic acid on luminal A breast cancer; a computational and experimental pharmacology approach

description: Breast cancer is a highly concerning and prevalent disease that impacts a significant proportion of women worldwide, whose repeated exposure to therapies leads to resistance for drugs; making it alarming to identify novel chemotherapeutic agents. Sinapic acid is a phenolic acid that occurs naturally and is known to exhibit cytotoxic action in a variety of cancer cell types. In the present study, we utilized cell cytotoxicity assays to assess the cytotoxic potential of sinapic acid on various breast cancer subtypes. In addition, we assessed the cell migration rate, cell apoptosis, and cell cycle phases. Moreover, we utilized multiple system biology tools to predict the potential targets, and molecular docking was performed on the hub targets followed by molecular dynamic (MD) simulations. Cytotoxicity assay was performed on cell lines MCF7, T47D, MDA-MB-468, and SKBR3 at different time exposures of 24, 48, and 96 h. Our results revealed sinapic acid to be potent on MCF7 and T47D cell lines. The cell cycle analysis and cell apoptotic assays revealed sinapic acid to cause cell death by apoptosis majorly in the G0/G1 phase. Computational biology revealed <i>KIF18B</i> and <i>VKORC1</i> to possess the highest binding affinity of −6.5 and −7.5 kcal/mol; displayed stable trajectories on MD run. The cytotoxicity of sinapic acid on luminal A cell lines may be due to the modulation of <i>VKORC1</i> and <i>KIF18B</i> with major cell death in the G0/G1 phase. However, the mechanism has been proposed <i>via in silico</i> tools, which need further validation using wet lab protocols. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24435096
title: Lead phytochemicals and marine compounds against ceruloplasmin in cancer targeting

description: <i>In silico</i> docking studies serve as a swift and efficient means to sift through a vast array of natural and synthetic small molecules, aiding in the identification of potential inhibitors for cancer biomarkers. One such biomarker, ceruloplasmin (CP), has been implicated in various tumor types due to its overexpression, earning it recognition as a marker of aggressive tumors. This study focused on pinpointing inhibitors for the CP –Myeloperoxidase (MPO) interaction site, a complex formation known to impede HOCl production, a crucial process for inducing apoptotic cell death in tumor cells. The initial phase of our investigation involved <i>in silico</i> docking studies, which screened a diverse library of phytochemicals and marine compounds. Through this process, we identified several promising drug candidates based on their binding affinities. Subsequently, these candidates underwent rigorous filtration based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties. Finally, we subjected the selected compounds to molecular dynamics (MDs) simulation to further assess their viability. Lycoperoside F, a steroidal alkaloid glycoside derived from tomatoes (Lycopersicon esculentum), stood out with notable interactions at the binding site. Another noteworthy compound was Xyloglucan (XG) oligosaccharides, predominantly found in the primary cell walls of higher plants. During the subsequent MDs simulations, these interactions were accompanied by highly stable root mean square deviation (RMSD) plots, signifying the consistency and robustness of the observed MDs behavior. XG oligosaccharides demonstrated the highest binding affinity with CP, reaffirming their potential as strong candidates. Additionally, Ardimerin digallate, known as a retroviral ribonuclease H inhibitor for HIV-1 and HIV-2, displayed favorable interactions at the MPO interaction site. Given that promising drug candidates must meet stringent criteria, including non-toxicity, effectiveness, specificity, stability and potency, these phytochemicals have the potential to progress to <i>in vitro</i> studies as CP inhibitors. Ultimately, this could contribute to the suppression of tumor growth, marking a significant step in cancer treatment research. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24435096.v1
title: Lead phytochemicals and marine compounds against ceruloplasmin in cancer targeting

description: <i>In silico</i> docking studies serve as a swift and efficient means to sift through a vast array of natural and synthetic small molecules, aiding in the identification of potential inhibitors for cancer biomarkers. One such biomarker, ceruloplasmin (CP), has been implicated in various tumor types due to its overexpression, earning it recognition as a marker of aggressive tumors. This study focused on pinpointing inhibitors for the CP –Myeloperoxidase (MPO) interaction site, a complex formation known to impede HOCl production, a crucial process for inducing apoptotic cell death in tumor cells. The initial phase of our investigation involved <i>in silico</i> docking studies, which screened a diverse library of phytochemicals and marine compounds. Through this process, we identified several promising drug candidates based on their binding affinities. Subsequently, these candidates underwent rigorous filtration based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties. Finally, we subjected the selected compounds to molecular dynamics (MDs) simulation to further assess their viability. Lycoperoside F, a steroidal alkaloid glycoside derived from tomatoes (Lycopersicon esculentum), stood out with notable interactions at the binding site. Another noteworthy compound was Xyloglucan (XG) oligosaccharides, predominantly found in the primary cell walls of higher plants. During the subsequent MDs simulations, these interactions were accompanied by highly stable root mean square deviation (RMSD) plots, signifying the consistency and robustness of the observed MDs behavior. XG oligosaccharides demonstrated the highest binding affinity with CP, reaffirming their potential as strong candidates. Additionally, Ardimerin digallate, known as a retroviral ribonuclease H inhibitor for HIV-1 and HIV-2, displayed favorable interactions at the MPO interaction site. Given that promising drug candidates must meet stringent criteria, including non-toxicity, effectiveness, specificity, stability and potency, these phytochemicals have the potential to progress to <i>in vitro</i> studies as CP inhibitors. Ultimately, this could contribute to the suppression of tumor growth, marking a significant step in cancer treatment research. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24452827
title: Identification of apposite antagonist for androgen receptor in prostate cancer: an in silico study of fenugreek compounds

description: Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from <i>Trigonella foenum-graecum</i>, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds’ maximum free binding energy (−103.3 ± 6, −87.4 ± 23, −68.5 ΔG<sub>bind</sub>) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24452827.v1
title: Identification of apposite antagonist for androgen receptor in prostate cancer: an in silico study of fenugreek compounds

description: Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from <i>Trigonella foenum-graecum</i>, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds’ maximum free binding energy (−103.3 ± 6, −87.4 ± 23, −68.5 ΔG<sub>bind</sub>) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24496342
title: Genetic insights into obesity: <i>in silico</i> identification of pathogenic SNPs in <i>MBOAT4</i> gene and their structural molecular dynamics consequences

description: Membrane Bound O-Acyltransferase Domain-Containing 4 (MBOAT4) protein catalyzes ghrelin acylation, leading to prominent ghrelin activity, hence characterizing its role as an anti-obesity target. We extracted 625 exonic SNPs from the ENSEMBL database and one phenotype-based missense mutation associated with obesity (A46T) from the HGMD (Human Gene Mutation Database). These were differentiated on deleterious missense SNPs of the <i>MBOAT4</i> gene through MAF (minor allele frequency: &lt;0.01) cut-off criteria in relation to some bioinformatics-based supervised machine learning tools. We found 8 rare-coding and harmful missense SNPs. The consensus classifier (<i>PredictSNP</i>) tool predicted that the SNP (G57S, C: rs561065025) was the most pathogenic. Several trained <i>in silico</i> algorithms have predicted decreased protein stability [ΔΔG (kcal/mol)] function in the presence of these rare-coding pathogenic mutations in the <i>MBOAT4</i> gene. Then, a stereochemical quality check (i.e. validation and assessment) of the 3D model was performed, followed by a blind cavity docking approach, used to search for druggable cavities and molecular interactions with citrus flavonoids of the <i>Rutaceae</i> family, ranked with energetic estimations. Significant interactions with <i>Phloretin 3',5'-Di-C-Glucoside</i> were also observed at R304, W306, N307, A311, L314 and H338 with (iGEMDOCK: −95.82 kcal/mol and AutoDock: −7.80 kcal/mol). The RMSD values and other variables of MD simulation analyses on this protein further validated its significant interactions with the above flavonoids. The <i>MBOAT4</i> gene and its molecular interactions could serve as an interventional future anti-obesity target. The current study’s findings will benefit future prospects for large population-based studies and drug development, particularly for generating personalized medicine. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24496342.v1
title: Genetic insights into obesity: <i>in silico</i> identification of pathogenic SNPs in <i>MBOAT4</i> gene and their structural molecular dynamics consequences

description: Membrane Bound O-Acyltransferase Domain-Containing 4 (MBOAT4) protein catalyzes ghrelin acylation, leading to prominent ghrelin activity, hence characterizing its role as an anti-obesity target. We extracted 625 exonic SNPs from the ENSEMBL database and one phenotype-based missense mutation associated with obesity (A46T) from the HGMD (Human Gene Mutation Database). These were differentiated on deleterious missense SNPs of the <i>MBOAT4</i> gene through MAF (minor allele frequency: &lt;0.01) cut-off criteria in relation to some bioinformatics-based supervised machine learning tools. We found 8 rare-coding and harmful missense SNPs. The consensus classifier (<i>PredictSNP</i>) tool predicted that the SNP (G57S, C: rs561065025) was the most pathogenic. Several trained <i>in silico</i> algorithms have predicted decreased protein stability [ΔΔG (kcal/mol)] function in the presence of these rare-coding pathogenic mutations in the <i>MBOAT4</i> gene. Then, a stereochemical quality check (i.e. validation and assessment) of the 3D model was performed, followed by a blind cavity docking approach, used to search for druggable cavities and molecular interactions with citrus flavonoids of the <i>Rutaceae</i> family, ranked with energetic estimations. Significant interactions with <i>Phloretin 3',5'-Di-C-Glucoside</i> were also observed at R304, W306, N307, A311, L314 and H338 with (iGEMDOCK: −95.82 kcal/mol and AutoDock: −7.80 kcal/mol). The RMSD values and other variables of MD simulation analyses on this protein further validated its significant interactions with the above flavonoids. The <i>MBOAT4</i> gene and its molecular interactions could serve as an interventional future anti-obesity target. The current study’s findings will benefit future prospects for large population-based studies and drug development, particularly for generating personalized medicine. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24475070
title: Synthesis, characterization, molecular docking and molecular dynamics simulations of novel 2,5-disubstituted-1,3,4-thiadiazole derivatives as potential cholinesterase/monoamine oxidase dual inhibitors for Alzheimer’s disease

description: Designing multi-targeted drugs (MTD) for Alzheimer’s disease (AD) is now one of the priorities for medicinal chemists, as the disease has a complicated not fully understood pathological nature and the approved mono-targeted drugs only alleviate the symptoms. In this study, the synthesis, spectral analyses and <i>in vitro</i> inhibition activity against cholinesterase (ChE) and monoamine oxidase (MAO) enzymes of a novel series of <i>N</i>-[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-2-(4-un/substituted) cyclic secondary amino-acetamide/propanamide derivatives were done. Generally, derivatives were more selective against acetylcholinesterase (AChE) and <i>h</i>-MAO-B than butyrylcholinesterase (BChE) and <i>h</i>-MAO-A, respectively. Derivatives <b>4a</b>, <b>4b</b>, <b>3a</b>, <b>3d</b> and <b>3b</b> ordered from the most potent to the least displayed significant inhibition against AChE. Also, derivatives <b>4a</b>, <b>4b</b> and <b>3a</b> still maintained their significant inhibition against <i>h</i>-MAO-B in the same potency order, making them dual inhibitors and MTD candidates for AD. Binding interactions with several crucial amino acid residues for activity and selectivity as well as the stability of the most active derivatives-enzyme complex were confirmed utilizing molecular docking and molecular dynamic simulation studies. Communicated by Ramaswamy H. Sarma Novel 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized. The ChEs/MAOs dual inhibition activity against Alzheimer’s disease was tested. Compounds <b>4a</b>, <b>4b</b> and <b>3a</b> were active dual inhibitor against both AChE and <i>h</i>-MAO-B. Compounds <b>3d</b> and <b>3b</b> were also active against AChE. No significant inhibition activity against BChE and <i>h</i>-MAO-A.
DOI: 10.6084/m9.figshare.24475070.v1
title: Synthesis, characterization, molecular docking and molecular dynamics simulations of novel 2,5-disubstituted-1,3,4-thiadiazole derivatives as potential cholinesterase/monoamine oxidase dual inhibitors for Alzheimer’s disease

description: Designing multi-targeted drugs (MTD) for Alzheimer’s disease (AD) is now one of the priorities for medicinal chemists, as the disease has a complicated not fully understood pathological nature and the approved mono-targeted drugs only alleviate the symptoms. In this study, the synthesis, spectral analyses and <i>in vitro</i> inhibition activity against cholinesterase (ChE) and monoamine oxidase (MAO) enzymes of a novel series of <i>N</i>-[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-2-(4-un/substituted) cyclic secondary amino-acetamide/propanamide derivatives were done. Generally, derivatives were more selective against acetylcholinesterase (AChE) and <i>h</i>-MAO-B than butyrylcholinesterase (BChE) and <i>h</i>-MAO-A, respectively. Derivatives <b>4a</b>, <b>4b</b>, <b>3a</b>, <b>3d</b> and <b>3b</b> ordered from the most potent to the least displayed significant inhibition against AChE. Also, derivatives <b>4a</b>, <b>4b</b> and <b>3a</b> still maintained their significant inhibition against <i>h</i>-MAO-B in the same potency order, making them dual inhibitors and MTD candidates for AD. Binding interactions with several crucial amino acid residues for activity and selectivity as well as the stability of the most active derivatives-enzyme complex were confirmed utilizing molecular docking and molecular dynamic simulation studies. Communicated by Ramaswamy H. Sarma Novel 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized. The ChEs/MAOs dual inhibition activity against Alzheimer’s disease was tested. Compounds <b>4a</b>, <b>4b</b> and <b>3a</b> were active dual inhibitor against both AChE and <i>h</i>-MAO-B. Compounds <b>3d</b> and <b>3b</b> were also active against AChE. No significant inhibition activity against BChE and <i>h</i>-MAO-A.
DOI: 10.6084/m9.figshare.24496341
title: Molecular interactions of cucurbitacins A and B with anaplastic lymphoma kinase for lung cancer treatment

description: Lung cancer is a major global public health issue and the leading cause of cancer-related deaths. Several medications are commonly used to treat lung cancer, either alone or in combination with other treatments. The anaplastic lymphoma kinase (ALK) protein is one of several target proteins that are thought to be potential therapeutic targets in the context of lung cancer. Several ALK inhibitors have been identified, but many of these have been associated with side effects and toxicity concerns. In this study, we intend to computationally predict the binding potential of cucurbitacins (CBNs), A and B to the active pockets of ALK, in order to estimate their potential ALK inhibitors. Compared to CBN-A, which has a binding energy of −7.9 kcal/mol, CBN B exhibits significantly better binding efficacy with a binding energy of −8.1 kcal/mol. This is closely comparable to the binding energy of Crizotinib, which is −8.2 kcal/mol. The results of the molecular dynamics simulation indicated that the docked complexes remained stable for the duration of the 100 ns simulation period. CBN inhibited the proliferation of both non-small cell lung cancer cell lines, H1299 and A549, in a dose-dependent manner. CBN-B inhibited the proliferation of lung cancer cells, showing IC50 values of 0.08 µM for H1299 cells and 0.10 µM for A549 cells. The computational analyses provide strong evidence that CBN-B has the potential to act as a potent natural inhibitor against ALK, and could prove to be a valuable treatment option for lung cancer. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24496341.v1
title: Molecular interactions of cucurbitacins A and B with anaplastic lymphoma kinase for lung cancer treatment

description: Lung cancer is a major global public health issue and the leading cause of cancer-related deaths. Several medications are commonly used to treat lung cancer, either alone or in combination with other treatments. The anaplastic lymphoma kinase (ALK) protein is one of several target proteins that are thought to be potential therapeutic targets in the context of lung cancer. Several ALK inhibitors have been identified, but many of these have been associated with side effects and toxicity concerns. In this study, we intend to computationally predict the binding potential of cucurbitacins (CBNs), A and B to the active pockets of ALK, in order to estimate their potential ALK inhibitors. Compared to CBN-A, which has a binding energy of −7.9 kcal/mol, CBN B exhibits significantly better binding efficacy with a binding energy of −8.1 kcal/mol. This is closely comparable to the binding energy of Crizotinib, which is −8.2 kcal/mol. The results of the molecular dynamics simulation indicated that the docked complexes remained stable for the duration of the 100 ns simulation period. CBN inhibited the proliferation of both non-small cell lung cancer cell lines, H1299 and A549, in a dose-dependent manner. CBN-B inhibited the proliferation of lung cancer cells, showing IC50 values of 0.08 µM for H1299 cells and 0.10 µM for A549 cells. The computational analyses provide strong evidence that CBN-B has the potential to act as a potent natural inhibitor against ALK, and could prove to be a valuable treatment option for lung cancer. Communicated by Ramaswamy H. Sarma
DOI: 10.15468/dl.x6ecc2
title: Occurrence Download

description: A dataset containing 1872 species occurrences available in GBIF matching the query:
{
 "TaxonKey" : [
 "is Rhaebo guttatus (Schneider, 1799)"
 ]
}

 The dataset includes 1872 records from 97 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0007141-241126133413365/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.15468/dl.btkrfv
title: Occurrence Download

description: A dataset containing 87 species occurrences available in GBIF matching the query:
{
 "and" : [
 "TaxonKey is Sarda orientalis (Temminck & Schlegel, 1844)",
 "Geometry POLYGON((170 20, 170 50, 120 50, 120 20, 170 20))",
 "HasCoordinate is true"
 ]
}

 The dataset includes 87 records from 11 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0007142-241126133413365/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.15468/dl.f2g7h2
title: Occurrence Download

description: A dataset containing 39 species occurrences available in GBIF matching the query:
{
 "and" : [
 {
 "and" : [
 "HasGeospatialIssue is false",
 "HasCoordinate is true",
 "OccurrenceStatus is Present",
 {
 "not" : {
 "BasisOfRecord" : [
 "is one of (Fossil, Living Specimen)"
 ]
 }
 }
 ]
 },
 "TaxonKey is one of (Rudbeckia laciniata var. hortensia L.H.Bailey)"
 ]
}

 The dataset includes 39 records from 14 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0007143-241126133413365/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.5281/zenodo.14246543
title: "TOʻDA-1 NEOLITHIC SITE STONE TOOLS"
DOI: 10.5281/zenodo.14246544
title: "TOʻDA-1 NEOLITHIC SITE STONE TOOLS"