Anticancer and DNA binding studies of potential amino acids based quinazolinone analogs: Synthesis, SAR and molecular docking

K P Rakesh; H K Kumara; H M Manukumar; D Channe Gowda

doi:10.1016/j.bioorg.2019.03.038

Anticancer and DNA binding studies of potential amino acids based quinazolinone analogs: Synthesis, SAR and molecular docking

Bioorg Chem. 2019 Jun:87:252-264. doi: 10.1016/j.bioorg.2019.03.038. Epub 2019 Mar 19.

Authors

K P Rakesh¹, H K Kumara¹, H M Manukumar¹, D Channe Gowda²

Affiliations

¹ Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India.
² Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, Karnataka, India. Electronic address: dchannegowda@yahoo.co.in.

PMID: 30908968
DOI: 10.1016/j.bioorg.2019.03.038

Abstract

A novel series of amino acids conjugated quinazolinone-Schiff's bases were synthesized and screened for their in vitro anticancer activity and validated by molecular docking and DNA binding studies. In the present investigations, compounds 32, 33, 34, 41, 42 and 43 showed most potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green comparing to doxorubicin and ethidium bromide as a positive control respectively. The structure-activity relationship (SAR) revealed that the tryptophan and phenylalanine derived electron donating groups (OH and OCH₃) favored DNA binding studies and anticancer activity whereas; electron withdrawing groups (Cl, NO₂, and F) showed least anticancer activity. The molecular docking study, binding interactions of the most active compounds 33, 34, 42 and 43 stacked with A-T rich regions of the DNA minor groove by surface binding interactions were confirmed.

Keywords: Amino acids; Anticancer; DNA binding; Docking study; Quinazolinone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Amino Acids / chemistry
Amino Acids / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Binding Sites / drug effects
Cell Line
Cell Proliferation / drug effects
DNA, Neoplasm / drug effects*
Dose-Response Relationship, Drug
Humans
MCF-7 Cells
Molecular Docking Simulation
Molecular Structure
Quinazolinones / chemical synthesis
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Structure-Activity Relationship

Substances

Amino Acids
Antineoplastic Agents
DNA, Neoplasm
Quinazolinones