Antiproliferative evaluations of triazoloquinazolines as classical DNA intercalators: Design, synthesis, ADMET profile, and molecular docking

Abstract

Novel triazoloquinazolines were designed and synthesized and evaluated as anticancer agents against HepG2 and HCT-116 cells. The biological testing data corresponded well to those of the molecular docking studies. The HCT-116 cell line was most affected due to the actions of our derivatives. Derivative 7 a was the most potent one against both HepG2 and HCT116 cells, with IC 50 = 7.98 and 5.57 µM, respectively. This compound showed anticancer activity that was nearly equipotent to that of doxorubicin against HepG2 cells, but higher than that of doxorubicin against HCT116 cells (IC 50 = 7.94 and 8.07 µM, respectively). Compounds 8, 7 b , and 6 f showed excellent anticancer activities against both the HCT116 and HepG2 cell lines. The highly active compounds 6 f , 7 a , 7 b , and 8 were evaluated for their DNAbinding activities. Compounds 7 a and 8 showed the highest binding activities. These derivatives potently intercalate in DNA, at IC 50 values of 42.90 and 48.13 µM, respectively. Derivatives 6 f and 7 b showed good DNA-binding activities, with IC 50 values of 54.24 and 50.56 µM, respectively. Furthermore, in silico calculated AD-MET profiles were established for our four highly active derivatives, in comparison to doxorubicin. Our derivatives 6 f , 7 a , 7 b , and 8 showed a very good ADMET profile.Compounds 6 f , 7 a , 7 b , and 8 follow Lipinski's rules, while doxorubicin violates three of these rules.

Semicarbazides Carrying Indole Core: Synthesis, Cytotoxicity Evaluation against Human Breast Cancer Cell Lines, and Molecular Modeling Studies

“…Besides its numerous biological effects such as antitubercular, [15] antioxidant, [16] and anti‐inflammatory, [17] semicarbazide is widely used as a strategic pharmacophore in the development of anticancer agents (Figure 2). [18–20] …”

“…Besides its numerous biological effects such as antitubercular, [15] antioxidant, [16] and anti-inflammatory, [17] semicarbazide is widely used as a strategic pharmacophore in the development of anticancer agents (Figure 2). [18][19][20] Molecular hybridization is a rational drug-design approach that involves the combination of at least two pharmacophores of different bioactive compounds in a single chemical entity. [21] This strategy mainly aims at the improvement of the biological activity profile of the end molecule compared to the parent ones.…”