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

• Published in: Bioorganic chemistry 2019-06, Vol.87, p.252-264
• Main Authors: Rakesh, K.P., Kumara, H.K., Manukumar, H.M., Channe Gowda, D.
• Format: Article
• Language: English
• Subjects: Amino acids; Anticancer; DNA binding; Docking study; Quinazolinone
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.03.038

[Display omitted] •Synthesis of potent quinazolinoe conjugated amino acids analogoues.•Compounds 32, 33, 34, 41, 42 and 43 showed potent anticancer activity.•EDGs showed more active than EWGs. 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.