Triazoloquinazoline derived classical DNA intercalators: Design, synthesis, in silico ADME profile, docking, and antiproliferative evaluations.

Thirteen novel [1,2,4]triazolo[4,3-c]quinazoline derivatives as DNA intercalators were synthesized and their anticancer activities evaluated against HepG2 and HCT-116 cells. A docking study was carried out to explore how the new derivatives bind to active sites of DNA. The docking data were highly interrelated with that of biological testing. The HCT-116 cell line was the most sensitive one to the effect of the new derivatives. Compound 7 _c exhibited the highest anticancer activities against both the HepG2 and HCT116 cancer cell lines. Despite this compound displaying less activity than doxorubicin, it could be useful as a template for future manipulation, optimization, and investigation to produce other analogs with potential activity. The most active derivatives, 7 _c , 7 _b , and 7 _a were evaluated as DNA binders. Compound 7 _c displayed the highest binding affinity. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile was calculated for the four most active compounds in comparison to doxorubicin as reference drug. Our derivatives 7 _a , 7 _b , and 7 _c displayed a very good calculated ADMET profile in comparison to doxorubicin.
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