Design, synthesis, molecular docking and biological evaluation of new carbazole derivatives as anticancer, and antioxidant agents.

Background: The carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities.
Objectives: This study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities.
Methods: The synthesized compounds were characterized utilizing HRMS, ¹ H-, and ¹³ C _APT -NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations.
Results: A series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2-5 against HepG2, HeLa, and MCF7 cancer cell lines with IC ₅₀ values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC ₅₀ value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC ₅₀ values in the range of 43.7-187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC ₅₀ values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively.
Conclusion: Most of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.
(© 2023. The Author(s).)