Title:Heterocyclic Moieties as HDAC Inhibitors: Role in Cancer Therapeutics
Volume: 22
Issue: 12
Author(s): Sharba Tasneem, Mohammad Mumtaz Alam*, Mohammad Amir, Mymoona Akhter, Suhel Parvez, Garima Verma, Lalit Mohan Nainwal, Ashif Equbal, Tarique Anwer and Mohammad Shaquiquzzaman*
Affiliation:
- Drug Design & Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education
and Research, Jamia Hamdard, New Delhi-110062, India
- Drug Design & Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education
and Research, Jamia Hamdard, New Delhi-110062, India
Keywords:
Histone deacetylase, histone deacetylase inhibitors, tubulin, cancer, structure-activity relationship, heterocyclic moieties.
Abstract: ‘Epigenetic’ regulation of genes via post-translational modulation of proteins is a wellexplored
approach for disease therapies, particularly cancer chemotherapeutics. Histone deacetylases
(HDACs) are one of the important epigenetic targets and are mainly responsible for balancing the
acetylation/deacetylation of lysine amino acids on histone/nonhistone proteins along with histone
acetyltransferase (HAT). HDAC inhibitors (HDACIs) have become important biologically active
compounds for the treatment of cancers due to cell cycle arrest, differentiation, and apoptosis in tumor
cells, thus leading to anticancer activity. Out of the four classes of HDAC, i.e., Class I, II, III, and IV,
HDACIs act on Class IV (Zinc dependent HDAC), and various FDA-approved drugs belong to this
category. The required canonical pharmacophore model (zinc-binding group, surface recognition cap,
and appropriate linker) supported by HDACIs, various heterocyclic moieties containing compounds
exhibiting HDAC inhibitory activity, and structure-activity relationship of different synthetic derivatives
reported during the last twelve years have been summarized in this review.