Design and synthesis of novel 2-(2-(4-bromophenyl)quinolin-4-yl)-1,3,4-oxadiazole derivatives as anticancer and antimicrobial candidates: in vitro and in silico studies

Abstract

Cancer is the second leading cause of death globally, surpassed only by heart disease. Moreover, bacterial infections remain a significant global health burden, contributing substantially to morbidity and mortality, especially among hospitalized patients. EGFR has emerged as a prime therapeutic target due to its pivotal role in driving uncontrolled cell growth and survival across numerous cancer types. In addition, DNA gyrase represents a promising target for the development of novel antimicrobial agents. Therefore, we aimed to design and synthesize new multi-target quinoline hybrids (7–17e) capable of acting as anti-proliferative and antimicrobial agents by inhibiting EGFR and microbial DNA gyrase, respectively. The inhibitory potential of the synthesized compounds was determined using in vitro and in silico approaches. The antiproliferative activity of the synthesized quinoline-oxadiazole derivatives 7–17e was assessed against two cancer cell lines, namely, hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7). The assessed compounds 7–17e showed considerable cytotoxic activity activities against HepG2 and MCF-7 with IC₅₀ values of 0.137–0.332 and 0.164–0.583 μg mL⁻¹, respectively, in comparison to erlotinib as the positive control, which showed an IC₅₀ value of 0.308 and 0.512 μg mL⁻¹, respectively. Moreover, an EGFR tyrosine kinase inhibition assay was conducted on the most prominent candidates. The results showed good IC₅₀ values of 0.14 and 0.18 μM for compounds 8c and 12d, respectively, compared to lapatinib (IC₅₀ value of 0.12 μM). Furthermore, the minimum antimicrobial inhibitory concentration was evaluated for the most prominent candidates with S. aureus, E. coli, and C. albicans. Compounds 17b, 17d and 17e displayed the most potent inhibitory activity, exhibiting 4-, 16- and 8-fold more activity, respectively, than the reference neomycin. Hence, we can conclude that the afforded compounds can be used as lead dual anticancer and antimicrobial candidates for future optimization.