RESUMO
BACKGROUND: A novel series of 1,3,4âoxadiazole connected to derivatives of quinazolinone (7a-e and 8a-f) was synthesized in the current investigation, and its anticancer and Topoisomeraseâ II inhibitory activity was evaluated. OBJECTIVE: These findings inspired the design, synthesis, and biological analysis of these 1,3,4âoxadiazole-quinazolinone analogues as antiproliferative TopoâII inhibitors. METHODS: The novel compound structures were determined using mass spectrometry and spectral methods (IR, NMR: 1H & 13C). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colourimetric assay has been used to evaluate the anticancer efficacy of these drugs, and Autodock 4.2 provides a description of the docking results. For the more active members, additional biological tests, such as the TopoâII inhibition experiment, were performed. These compounds' physicochemical and ADMET characteristics were examined in more detail. RESULTS: In the experiment for antiproliferative activity, compounds 7d, 7e, 8c, 8e, and 8f demonstrated encouraging cytotoxicity findings against HCTâ116 and HepG2 cancer cell lines, with IC50 values ranging from 3.85 to 19.43 µM. Compounds 7d, 7e, and 8e were the most potent inhibitors of Topo II with IC50 values of 15.18, 17.55, and 12.59 µM, respectively. Additionally, the docked compound 8c showed the strongest conventional hydrogen bonds among the residues Leu507(B), Asn508(B), Asn520(B), and Glu522(B) in the Human topoisomeraseâIIß active site in the DNA complex (4G0U) when compared to the findings of docking experiments. CONCLUSIONS: New findings have discovered the fact that fused 1,3,4âoxadiazole bearing quinazolinone contributed great significance in the field of medicinal chemistry due to their diverse biological properties. Finally, the in silico pharmacokinetic profile of all the synthesized derivatives was estimated using SwissADME, where some of the compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation. The result of this activity advises that with a simple modification in structure, a potent anticancer agent can be generated with good efficacy.