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Searching for Potential HDAC2 Inhibitors: Structure-activity Relationship Studies on Indole-based Hydroxamic Acids as an Anticancer Agent
- Source :
- Letters in Drug Design & Discovery. 17:905-917
- Publication Year :
- 2020
- Publisher :
- Bentham Science Publishers Ltd., 2020.
-
Abstract
- Aim: To predict the most potent indole based HDAC2 inhibitors from several scientific reports through the process of lead identification and SAR development. Background: The current scenario is observing Histone Deacetylase (HDAC) as an alluring molecular target for the designing and development of drugs for cancer treatment. Background: The current scenario is observing Histone Deacetylase (HDAC) as an alluring molecular target for the designing and development of drugs for cancer treatment. Objective: To identify the lead and establish structure-activity correlation among indole based hydroxamic acid to find out promising HDAC2 based anticancer agent. Methods: A dataset containing 59 molecules was analyzed using structure and ligand-based integrated approach comprising atom-based 3D-QSAR (Quantitative Structure-Activity Relationship) and pharmacophore study, e-pharmacophore mapping and molecular modeling methodologies. The finest model was prepared by amalgamating the properties of electronegativity, polarizability, Vander Waals forces and other conformational aspects. Results: The result of 3D QSAR analysis, performed for 4 PLS factor, provided the following statistical information: R2 = 0.9461, Q2 = 0.7342 and low standard of deviation SD = 0.1744 for hypothesis ADDDH.10 and R2 = 0.9444, Q2= 0.7858 and again low standard of deviation SD = 0.1795 for hypothesis DDHRR.12. The XP molecular docking showed intermolecular interactions of small molecules with amino acids such as GLY154, HIP145, PHE210, HIE183, internal H2O and Zn2+. Conclusion: The interpretation of data generated as a result of this investigation clearly hints about the better biological activity of test compounds as compared to SAHA. Hence, the outcome of these structure and ligand-based integrated studies could be employed for the design of novel arylindole derivatives as a potent HDAC inhibitor.
- Subjects :
- Indole test
0303 health sciences
010405 organic chemistry
Chemistry
Histone deacetylase 2
Pharmaceutical Science
01 natural sciences
Combinatorial chemistry
0104 chemical sciences
03 medical and health sciences
Drug Discovery
Molecular Medicine
Structure–activity relationship
030304 developmental biology
Subjects
Details
- ISSN :
- 15701808
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Letters in Drug Design & Discovery
- Accession number :
- edsair.doi...........437804b6673a7b6a7a04705eb1c05fc6