{"title":"基于集成结构和配体方法的构效关系探索:基于羟肟酸的HDAC抑制剂和细胞毒性药物。","authors":"Ekta Shirbhate, Jaiprakash Pandey, Vijay Kumar Patel, Ravichandran Veerasamy, Harish Rajak","doi":"10.4274/tjps.galenos.2022.12269","DOIUrl":null,"url":null,"abstract":"<p><p>The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for histone deacetylase (HDAC) inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anticancer activity. We have selected a dataset from earlier research findings. The target and ligand molecules were procured from recognized databases and incorporated into pivotal findings such as molecular docking (XP glide), e-pharmacophore study and 3D QSAR model designing study (phase). Docking revealed molecule 39 with better docking score and well binding contact with the protein. 3D QSAR analysis, which was performed for partial least squares factor 5 reported good 0.9877 and 0.7142 as R2 and Q2 values and low standard of deviation: 0.1049 for hypothesis AADRR.139. Based on the computational outcome, it has been concluded that molecule 39 is an effective and relevant candidate for inhibition of HDAC activity. Moreover, these computational approaches motivate to discover novel drug candidates in pharmacological and healthcare sectors.</p>","PeriodicalId":23378,"journal":{"name":"Turkish Journal of Pharmaceutical Sciences","volume":"20 4","pages":"270-284"},"PeriodicalIF":1.8000,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445225/pdf/TJPS-20-270.pdf","citationCount":"1","resultStr":"{\"title\":\"Exploration of Structure-Activity Relationship Using Integrated Structure and Ligand Based Approach: Hydroxamic Acid-Based HDAC Inhibitors and Cytotoxic Agents.\",\"authors\":\"Ekta Shirbhate, Jaiprakash Pandey, Vijay Kumar Patel, Ravichandran Veerasamy, Harish Rajak\",\"doi\":\"10.4274/tjps.galenos.2022.12269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for histone deacetylase (HDAC) inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anticancer activity. We have selected a dataset from earlier research findings. The target and ligand molecules were procured from recognized databases and incorporated into pivotal findings such as molecular docking (XP glide), e-pharmacophore study and 3D QSAR model designing study (phase). Docking revealed molecule 39 with better docking score and well binding contact with the protein. 3D QSAR analysis, which was performed for partial least squares factor 5 reported good 0.9877 and 0.7142 as R2 and Q2 values and low standard of deviation: 0.1049 for hypothesis AADRR.139. Based on the computational outcome, it has been concluded that molecule 39 is an effective and relevant candidate for inhibition of HDAC activity. Moreover, these computational approaches motivate to discover novel drug candidates in pharmacological and healthcare sectors.</p>\",\"PeriodicalId\":23378,\"journal\":{\"name\":\"Turkish Journal of Pharmaceutical Sciences\",\"volume\":\"20 4\",\"pages\":\"270-284\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10445225/pdf/TJPS-20-270.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Turkish Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4274/tjps.galenos.2022.12269\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Turkish Journal of Pharmaceutical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4274/tjps.galenos.2022.12269","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Exploration of Structure-Activity Relationship Using Integrated Structure and Ligand Based Approach: Hydroxamic Acid-Based HDAC Inhibitors and Cytotoxic Agents.
The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for histone deacetylase (HDAC) inhibitors and correlate their physicochemical, steric, and electrostatic properties with their anticancer activity. We have selected a dataset from earlier research findings. The target and ligand molecules were procured from recognized databases and incorporated into pivotal findings such as molecular docking (XP glide), e-pharmacophore study and 3D QSAR model designing study (phase). Docking revealed molecule 39 with better docking score and well binding contact with the protein. 3D QSAR analysis, which was performed for partial least squares factor 5 reported good 0.9877 and 0.7142 as R2 and Q2 values and low standard of deviation: 0.1049 for hypothesis AADRR.139. Based on the computational outcome, it has been concluded that molecule 39 is an effective and relevant candidate for inhibition of HDAC activity. Moreover, these computational approaches motivate to discover novel drug candidates in pharmacological and healthcare sectors.