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

BMC Chemistry

Research

Refik Servi¹  İrfan Koca²  İrfan Çapan³  Nidal Jaradat⁴  Mohammed Hawash⁴  Yusuf Sert⁵ 

[1] Department of Anatomy, Faculty of Medicine, Firat University, Elazig, Turkey;Department of Chemistry, Faculty of Art & Sciences, Yozgat Bozok University, Yozgat, Turkey;Department of Material and Material Processing Technologies, Gazi University, Technical Sciences Vocational College, 06560, Ankara, Turkey;Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, 00970, Nablus, Palestine;Yozgat Bozok University, Sorgun Vocational School, Yozgat, Turkey;

关键词: Carbazole;    Anticancer;    Antifibrotic;    LX-2;    Antioxidant;    Doxorubicin;    Molecular docking;   

DOI  :  10.1186/s13065-023-00961-y

 received in 2022-12-09, accepted in 2023-05-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities.ObjectivesThis study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities.MethodsThe synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-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.ResultsA 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 IC50 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 IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 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 IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively.ConclusionMost 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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