Design, synthesis, anticancer evaluation and molecular docking studies of different aryl derivatives of azaindole-pyrimidine-1,3,4-oxadiazoles

The aryl-azaindole-pyrimidine-1,3,4-oxadiazole derivatives (12a–j) were synthesized by Suzuki coupling reaction between bromo-azaindole-1,3,4-oxadiaole intermediate 10 and various aryl boronic acids (11a–j) by using of Pd(dppf)Cl2 and K2CO3 in 1,4-dioxane/H2O. Here, the Suzuki coupling mechanism starts with the oxidative addition followed by transmetallation and ends with reductive elimination. These derivatives were screened in vitro anticancer applications against four human cancer cell lines including MCF-7, A549, Colo-205, and A2780 by employing of MTT method, the well-known chemotherapeutic agent as etoposide used as positive control. Among them, compound 12a bearing 3,4,5-trimethoxy substituent on the aryl moiety displayed good activity as compared with positive control against MCF-7, A549, Colo-205, and A2780 cell lines with IC50 values of 1.10 ± 0.84 µM, 1.07 ± 0.067 µM, 1.20 ± 0.95 µM, and 1.34 ± 0.66 µM respectively. Compounds 12a and 12b primarily engage in hydrophobic interactions such as pi-pi stacked, amide-pi stacked, pi-alkyl, and alkyl interactions. Specifically, nucleotides DG13, DA12, and arg503 display pi-pi stacked and amide-pi stacked interactions.