Current computer-aided drug design最新文献

{"title":"Uncovering the Mechanisms of Cinnamic Acid Treating Diabetic Nephropathy Based on Network Pharmacology, Molecular Docking, and Experimental Validation.","authors":"Limiao Dai, Yang He, Siqiang Zheng, Jiyu Tang, Lanjun Fu, Li Zhao","doi":"10.2174/0115734099286283240130115111","DOIUrl":"https://doi.org/10.2174/0115734099286283240130115111","url":null,"abstract":"<p><strong>Background: </strong>Cinnamic acid (Cinn) is a phenolic acid of Cinnamomum cassia (L.) J. Presl. that can ameliorate diabetic nephropathy (DN). However, comprehensive therapeutic targets and underlying mechanisms for Cinn against DN are limited.</p><p><strong>Objective: </strong>In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy.</p><p><strong>Methods: </strong>The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn.</p><p><strong>Results: </strong>Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice.</p><p><strong>Conclusion: </strong>This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Fingerprints and Data Mining-based Prediction of Some Bioactive Compounds from Allium sativum as Histone Deacetylase 9 (HDAC9) Inhibitors.","authors":"Totan Das, Arijit Bhattacharya, Tarun Jha, Shovanlal Gayen","doi":"10.2174/0115734099282303240126061624","DOIUrl":"https://doi.org/10.2174/0115734099282303240126061624","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylase 9 (HDAC9) is an important member of the class IIa family of histone deacetylases. It is well established that over-expression of HDAC9 causes various types of cancers including gastric cancer, breast cancer, ovarian cancer, liver cancer, lung cancer, lymphoblastic leukaemia, etc. The important role of HDAC9 is also recognized in the development of bone, cardiac muscles, and innate immunity. Thus, it will be beneficial to find out the important structural attributes of HDAC9 inhibitors for developing selective HDAC9 inhibitors with higher potency.</p><p><strong>Methods: </strong>The classification QSAR-based methods namely Bayesian classification and recursive partitioning method were applied to a dataset consisting of HADC9 inhibitors. The structural features strongly suggested that sulphur-containing compounds can be a good choice for HDAC9 inhibition. For this reason, these models were applied further to screen some natural compounds from Allium sativum. The screened compounds were further accessed for the ADME properties and docked in the homology-modelled structure of HDAC9 in order to find important amino acids for the interaction. The best-docked compound was considered for molecular dynamics (MD) simulation study.</p><p><strong>Results: </strong>The classification models have identified good and bad fingerprints for HDAC9 inhibition. The screened compounds like ajoene, 1,2 vinyl dithiine, diallyl disulphide and diallyl trisulphide had been identified as compounds having potent HDAC9 inhibitory activity. The results from ADME and molecular docking study of these compounds show the binding interaction inside the active site of the HDAC9. The best-docked compound ajoene shows satisfactory results in terms of different validation parameters of MD simulation study.</p><p><strong>Conclusion: </strong>This in-silico modelling study has identified the natural potential lead (s) from Allium sativum. Specifically, the ajoene with the best in-silico features can be considered for further in-vitro and in-vivo investigation to establish as potential HDAC9 inhibitors.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Status and Prospects of Research on Deep Learning-based De Novo Generation of Drug Molecules.","authors":"Huanghao Shi, Zhichao Wang, Litao Zhou, Zhiwang Xu, Liangxu Xie, Ren Kong, Shan Chang","doi":"10.2174/0115734099287389240126072433","DOIUrl":"https://doi.org/10.2174/0115734099287389240126072433","url":null,"abstract":"<p><p>Traditional molecular de novo generation methods, such as evolutionary algorithms, generate new molecules mainly by linking existing atomic building blocks. The challenging issues in these methods include difficulty in synthesis, failure to achieve desired properties, and structural optimization requirements. Advances in deep learning offer new ideas for rational and robust de novo drug design. Deep learning, a branch of machine learning, is more efficient than traditional methods for processing problems, such as speech, image, and translation. This study provides a comprehensive overview of the current state of research in de novo drug design based on deep learning and identifies key areas for further development. Deep learning-based de novo drug design is pivotal in four key dimensions. Molecular databases form the basis for model training, while effective molecular representations impact model performance. Common DL models (GANs, RNNs, VAEs, CNNs, DMs) generate drug molecules with desired properties. The evaluation metrics guide research directions by determining the quality and applicability of generated molecules. This abstract highlights the foundational aspects of DL-based de novo drug design, offering a concise overview of its multifaceted contributions. Consequently, deep learning in de novo molecule generation has attracted more attention from academics and industry. As a result, many deep learning-based de novo molecule generation types have been actively proposed.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR Kinase Inhibiting Amino-enones for Breast Cancer; CADD Approach.","authors":"Deena Gladies Raymond Mohanraj, Manikandan Alagumuthu, Subha Chellam, Abishek Suresh Kumar, Tejaswini Nagaraj Poojari, Jeevitha Suresh Kumar, Palaniraja Subramaniam","doi":"10.2174/0115734099266822231219073332","DOIUrl":"https://doi.org/10.2174/0115734099266822231219073332","url":null,"abstract":"<p><strong>Background: </strong>The Computer-Aided Drug Discovery (CADD) approach was used to develop a few Epidermal Growth Factor Receptor (EGFR) kinase inhibitors. EGFR kinase expression is highly associated with genomic instability, higher proliferation, lower hormone receptor levels, and HER2 over-expression. It is more common in breast cancer. Thus, EGFR Kinase is one of the main targets in discovering new cancer medicine.</p><p><strong>Objective: </strong>To computationally validate some amides substituted β-amino enones as EGFR inhibitors and to carry out associated in vitro anticancer agents.</p><p><strong>Methods: </strong>We used tools such as molecular docking, MD simulations, DFT calculations, and ADMET predictions in silico to establish a preliminary SAR. In vitro, we used BT474 (ER+HER2+) and MCF-7 (ER-HER2) cell lines along with normal breast cell epithelial cells (MFC-10a) for anticancer studies and EGFR kinase inhibition assay studies. As the Reactive Oxygen Species (ROS) plays the main role in cancer development, we also analyzed the antioxidant potentials of these compounds.</p><p><strong>Results: </strong>Among the family of eleven amides substituted (Z)-β-amino enones (5a-k), compounds 5b, 5c, 5g, and 5h showed valuable in silico and in vitro bio-activity. Remarkably, the in-silico results almost coincided with in vitro study results.</p><p><strong>Conclusion: </strong>We recommend compounds 5b, 5c, 5g, and 5h for pre-clinical and clinical evaluation to establish them as future cancer therapeutics.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An In silico Study on B-cell Epitope Mapping of Acinetobacter baumannii Outer Membrane Protein K.","authors":"Hana Heidarinia, Keyghobad Ghadiri, Fatemeh Nemati Zargaran, Roya Chegene Lorestani, Mosayeb Rostamian","doi":"10.2174/0115734099281401240118054834","DOIUrl":"https://doi.org/10.2174/0115734099281401240118054834","url":null,"abstract":"<p><strong>Background: </strong>Acinetobacter baumannii is one of the main causes of nosocomial infections. No vaccine has yet been licensed for use in humans, and efforts are still ongoing.</p><p><strong>Objective: </strong>In the present study, we have predicted the B-cell epitopes of A. baumannii's outer membrane protein K (OMPK) by using epitope prediction algorithms as possible vaccine candidates for future studies.</p><p><strong>Methods: </strong>The linear B-cell epitopes were predicted by seven different prediction tools. The 3D structure of OMPK was modeled and used for discontinuous epitope prediction by ElliPro and DiscoTope 2.0 tools. The final linear epitopes and the discontinuous epitope segments were checked for potential allergenicity, toxicity, human similarity, and experimental records. The structure and physicochemical features of the final epitopic peptide were assessed by numerous bioinformatics tools.</p><p><strong>Results: </strong>Many B-cell epitopes were detected that could be assessed for possible antigenicity and immunogenicity. Also, an epitopic 22-mer region (peptide) of OMPK was found that contained both linear and discontinuous B-cell epitopes. This epitopic peptide has been found to possess appropriate physicochemical and structural properties to be an A. baumannii vaccine candidate.</p><p><strong>Conclusion: </strong>Altogether, here, the high immunogenic B-cell epitopes of OMPK have been identified, and a high immunogenic 22-mer peptide as an A. baumannii vaccine candidate has been introduced. The in vitro/in vivo studies of this peptide are recommended to decide its real efficacy and efficiency.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing Drug Delivery Vehicles based on N-(2-Hydroxypropyl) Methacrylamide.","authors":"Ramakrishna Prasad Are, Anju R Babu","doi":"10.2174/0115734099278986231228070823","DOIUrl":"https://doi.org/10.2174/0115734099278986231228070823","url":null,"abstract":"<p><strong>Background: </strong>The development of polymeric-based drug delivery has seen faster growth in the past two decades. In polymers, copolymers as drug carriers are increasing to decrease the drug compounds' side effects and dosage-related toxicity.</p><p><strong>Objectives: </strong>The study's primary objective is to utilize computational resources to design drug molecules and perform in silco physicochemical property analysis. In our study, we designed new copolymers based on N-(2-Hydroxypropyl) methacrylamide (HPMA) as backbone along with polyethylene glycol (PEG) and lauryl methacrylate (LMA).</p><p><strong>Methods: </strong>Different functional groups were selected for attaching to the side chain of the copolymers through a random trial and error approach. In order to predict the pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity), the designed copolymer molecules were evaluated utilizing ADME and PkCSM pharmacokinetics servers. Molecular interaction between the designed copolymer molecules and human serum albumin (HSA) was performed using AutoDock Vina and PatchDock server.</p><p><strong>Results: </strong>The designed molecules are shown to be soluble in water and have high gastrointestinal absorption. Only one molecule is predicted to pass through the blood-brain barrier. Two designed molecules have been shown to have carcinogenic properties. Lethal dose 50 (LD50), cytochrome P450, and permeability glycoprotein Enzyme's substrate formation were also analyzed for toxicity and metabolism.</p><p><strong>Conclusion: </strong>Our study will provide insight for designing new drug compounds or carriers and analyzing their physicochemical properties to help further optimize compounds for clinical studies.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragaloside IV Overcomes Anlotinib Resistance in Non-small Cell Lung Cancer through miR-181a-3p/UPR-ERAD Axis.","authors":"Lihuai Wang, Tonglin Sun, Xiao Yang, Zhi Wen, Yinhui Sun, Hua Liu","doi":"10.2174/0115734099252873231117072107","DOIUrl":"https://doi.org/10.2174/0115734099252873231117072107","url":null,"abstract":"<p><strong>Background: </strong>Astragaloside IV (AS-IV) has been shown to have a curative effect on non-small cell lung cancer (NSCLC). This study aimed to elucidate the role of AS-IV in NSCLC cell anlotinib resistance (AR).</p><p><strong>Methods: </strong>The NSCLC/AR cells, resistant to anlotinib, have been produced. The role of AS-IV in the AR of NSCLC cells about the miR-181a-3p/unfolded protein response (UPR)- endoplasmic reticulum associated degradation (ERAD) pathway was then discussed by treating the cells with anlotinib or AS-IV, or by manipulating them with inhibitors or mimics of miR- 181a-3p, HRD1 or Derlin-1 overexpression plasmids.</p><p><strong>Results: </strong>We found that AS-IV could suppress the AR of NSCLC cells. In addition, miR-181a- 3p was elevated in NSCLC/AR cells. Functionally, AS-IV limited the AR of NSCLC cells by reducing miR-181a-3p. Further, activation of the UPR-ERAD pathway was correlated with AR in NSCLC cells. Increased sensitivity of NSCLC cells to anlotinib caused by miR-181a-3p inhibitor could be reversed by overexpression of HRD1 or Derlin-1.</p><p><strong>Conclusion: </strong>This research revealed a promising NSCLC/AR treatment approach by showing that AS-IV exposed NSCLC cells to anlotinib by inhibiting the miR-181a-3p/UPR-ERAD axis.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of the Effect of Scopolamine on Breast Cancer: Determination by Network Pharmacology and Bioinformatics.","authors":"Yang Xiao, Qiang Guo, Yichen Li, Mengcong Ma, Yu Sun, Qing Gu, Yunfeng Xiao","doi":"10.2174/0115734099281860231221084102","DOIUrl":"https://doi.org/10.2174/0115734099281860231221084102","url":null,"abstract":"<p><strong>Background: </strong>To a certain extent, traditional Chinese medicine (TCM)-based anesthesia has replaced opiate administration in recent years. Preliminary drug screening has revealed that scopolamine may affect breast cancer (BC) metastasis by an unknown mechanism.</p><p><strong>Methods: </strong>Network pharmacology, bioinformatics, and protein-protein interaction (PPI) topological analysis were implemented to identify the core genes linking scopolamine and BC. The core genes were then subjected to gene expression profiling interactive analysis (GEPIA). The top ten pathways were detected by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The impact of immune infiltration on the core gene difference and survival analyses was then determined. Molecular docking was then performed on the core genes and the main active components.</p><p><strong>Results: </strong>Protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), heat shock protein 90 alpha class A (HSP90AA1), caspase 3 (CASP3), and estrogen receptor 1 (ESR1) were the key genes in the interaction between scopolamine and BC cells. The KEGG enrichment analysis disclosed that the top ten pathways significantly associated with the scopolamine response in BC included \"protein glycosylation,\" \"phosphoinositide 3-kinase (PI3K)-Akt signaling,\" \"mitogen- activated protein kinase (MAPK) signaling\" and others. The AKT1, EGFR, and especially the HSP90AA1 expression levels were correlated with survival in patients with BC. Immune infiltration also influenced the survival outcome. Molecular docking demonstrated that scopolamine bound and formed stable complexes with the protein products of all five aforementioned genes.</p><p><strong>Conclusion: </strong>Scopolamine has multiple targets regulating BC cell function and may increase the risk of metastasis during treatment. Therefore, it should be preoperatively administered with caution to patients with BC.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-based Virtual Screening of Traditional Chinese Medicine and the Discovery of Novel Inhibitors of TCTP.","authors":"Juxia Bai, Yangyang Ni, Yuqi Zhang, Junfeng Wan, Liqun Liang, Haoran Qiao, Yanyan Zhu, Qingjie Zhao, Huiyu Li","doi":"10.2174/0115734099277605231218071503","DOIUrl":"https://doi.org/10.2174/0115734099277605231218071503","url":null,"abstract":"<p><strong>Background: </strong>Translationally controlled tumour protein (TCTP) is associated with tumor diseases, such as breast cancer, and its inhibitor can reduce the growth of tumor cells. Unfortunately, there is currently no effective medication available for treating TCTP-related breast cancer.</p><p><strong>Objective: </strong>The objective of this study was to explore the inhibitor candidates among natural compounds for the treatment of breast cancer related to TCTP protein.</p><p><strong>Methods: </strong>To explore the potential inhibitors of TCTP, we first screened out four potential inhibitors in the Traditional Chinese Medicine (TCM) for cancer based on AI virtual screening using the docking method, and then revealed the interaction mechanism of TCTP and four candidate inhibitors from TCM with molecular docking and molecular dynamics (MD) methods.</p><p><strong>Results: </strong>Based on the conformational characteristics and the MD properties of the four leading compounds, we designed the new skeleton molecules with the AI method using MolAICal software. Our MD simulations have revealed that different small molecules bind to different sites of TCTP, but the flexible regions and the signaling pathways are almost the same, and the VDW and hydrophobic interactions are crucial in the interactions between TCTP and ligands.</p><p><strong>Conclusion: </strong>We have proposed the candidate inhibitor of TCTP. Our study has provided a potential new method for exploring inhibitors from Traditional Chinese Medicine (TCM).</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139682148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Marine Bioactive Compound as Potential Multiple Inhibitors in Triple-negative Breast Cancer - An in silico Approach.","authors":"Hema Priya Manivannan, Vishnu Priya Veeraraghavan, Arul Prakash Francis","doi":"10.2174/0115734099287118240102112337","DOIUrl":"https://doi.org/10.2174/0115734099287118240102112337","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer lacking specific receptors, with dysregulated and overactivated Hedgehog (Hh) and mTOR/PI3K/AKT signaling pathways as potential therapeutic targets.</p><p><strong>Objective: </strong>This study aimed to identify potential inhibitors among 53 alkaloids derived from 9 marine bryozoans using in silico approaches. It sought to analyze their impact on key signaling targets and their potential for future experimental validation.</p><p><strong>Methods: </strong>In this research, selected targets were evaluated for protein-protein interactions, coexpression survival, and expression profiles. The protein expression was validated through the Human Protein Atlas (HPA) database and druggability through DGIdb. Online web servers were employed to assess drug-likeness, physiochemical properties, pharmacokinetics, and toxicological characteristics of the compounds. Molecular docking and dynamic simulations were carried out for ligand-protein interactions. Common Pharmacophore features, bioavailability, bioactivity, and biological activity spectrum (BAS) were also analyzed.</p><p><strong>Results: </strong>Out of the 13 compounds studied, 10 displayed strong binding affinity with binding energies ranging from >-6.5 to <-8 Kcal/mol across all targets. Molecular dynamics simulations provided insights into Amathamide E's stability and conformational changes. Pharmacophore modeling revealed common features in 14 compounds potentially responsible for their biological activity.</p><p><strong>Conclusion: </strong>Our findings indicate the potential of marine-derived compounds as TNBC inhibitors. Further in vitro and in vivo validation is necessary to establish their effectiveness and explore their role as novel anti-TNBC agents.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139479686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}