Quinoline-linked 1,2,3-Triazole Hybrids: Design, Synthesis, Anticancer Activity and Computational Investigations

Synthesized a library of new quinoline-based 1,2,3-triazole scaffolds involving Suzuki-Miyaura cross-coupling and metal-free multicomponent reactions. Evaluated their in vitro anticancer activities against human breast (MCF-7), lung (A-549) and liver (HepG2) cancer cell lines with reference to Doxorubicin as standard. Four compounds 5a, 5d, 5e and 5f displayed outstanding activity against all three cell lines. Compound 5a, showcasing -Cl in the R₂ position of the phenyl ring demonstrated potent activity with IC₅₀ values of 9.25 ± 0.22, 9.56 ± 0.19 and 10.56 ± 0.19 µM against MCF-7, A-549 and HepG2 cell lines respectively. The compound 5f, containing m-Cl and m-OMe groups in R₁ and R₂ positions demonstrated potent activity with IC₅₀ values of 10.49 ± 0.31 (MCF-7), 10.27 ± 0.27 (A-549) and 11.27 ± 0.30 µM (HepG2). Compound 5f with -Cl and -I group presented potent activity with an IC₅₀ value of 11.40 ± 0.29 (MCF-7), 10.42 ± 0.21 (A-549) and 12.32 ± 0.33 µM (HepG2). Compound 5d gave out a potent activity with IC₅₀ values of 10.42 ± 0.25 (MCF-7), 12.97 ± 0.22 (A-549) and 13.05 ± 0.45 µM (HepG2). Toxicity results against Hek-293 proved that these compounds were not harmful. The computational screening of these compounds revealed favourable drug-likeness properties and important binding interactions against Fibroblast Growth Factor Receptor 1.