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.
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.