Design, synthesis, and antitumor evaluation of quinoline‐imidazole derivatives

Abstract

A series of compounds bearing quinoline-imidazole (8a-e, 9a-e, 10a-e, 11a-e, and 12a-e) not reported previously were designed and synthesized. The target compounds were evaluated for antitumor activity against A549, PC-3, HepG2, and MCF-7 cells by the MTT method, with NVP-BEZ235 being the positive control. Most compounds showed moderate activity and compound 12a showed the best activity against HepG2, A549, and PC-3 cells, with half-maximal inhibitory concentration (IC ) values of 2.42 ± 1.02 µM, 6.29 ± 0.99 µM, and 5.11 ± 1.00 µM, respectively, which was equal to NVP-BEZ235 (0.54 ± 0.13 µM, 0.36 ± 0.06 µM, 0.20 ± 0.01 µM). Besides, the IC value of 12a against the cell line WI-38 (human fetal lung fibroblasts) was 32.8 ± 1.23 µM, indicating that the target compounds were selective for cancer cells. So, 11a and 12a were evaluated against PI3Kα and mTOR to find out if the compounds acted through the PI3K-Akt-mTOR signal transduction pathway. The inhibition ratios to PI3Kα and mTOR were slightly lower than that of NVP-BEZ235, suggesting there may be some other mechanisms of action. The structure-activity relationships and docking study of 11a and 12a revealed that the latter was superior. Moreover, the target compounds showed better in vitro anticancer activity when the C-6 of the quinoline ring was replaced by a bromine atom.

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

“…Recently, new series of imidazo[4,5- c ]quinoline derivatives have been reported in the literature as PI3K/mTOR inhibitors. Xiao et al proved anticancer properties of a set of quinoline molecules, from which compound 39 ( Figure 13 ) is the most active, with a mTOR IC 50 value of 1.4 μM and PI3Kα IC 50 of 0.9 μM [ 102 ].…”

Silver‐Catalyzed [3+1+1] Annulation of Nitrones with Isocyanoacetates as an Approach to 1,4,5‐Trisubstituted Imidazoles

“…Polysubstituted imidazoles constitute a ubiquitous class of five‐membered nitrogen‐containing heterocyclic compounds featured in various bioactive natural products and pharmaceuticals, [1,2] including antitumor, [3] antiviral, [4] antifungal [5] and antibacterial [6] agents (Figure 1). Over the years, efficient and versatile transition metal‐catalyzed methods for the synthesis of such heterocycles have been developed [2,7] .…”

Synthesis, Characterization, and Anticancer Studies of Some Pyrazole‐Based Hybrid Heteroatomics

“…Quinolineimidazole derivatives showed antitumor activity on A549 and MCF-7 cell lines with better activity when a bromine atom replaced the C-6 of the quinoline ring. [20] Pyrrole-imidazole derivatives showed potent cytotoxicity against human pancreatic cancer cell line, PANC-1. [21] Our synthesized derivatives showed good anticancer activity on A549 cells with lower IC 50 values.…”