Synthesis and biological assessment of indole derivatives containing penta-heterocycles scaffold as novel anticancer agents towards A549 and K562 cells

Abstract

Herein, a new series of 2-chloro-N-(5-(2-oxoindolin-3-yl)-4H-pyrazol-3-yl) acetamide derivatives containing 1,3,4-thiadiazole (10a–i) and 4H-1,2,4-triazol-4-amine (11a–r) moiety was designed, synthesised as novel anticancer agents. The antiproliferative activity values indicated that compound 10 b stood as the most potent derivative with IC₅₀ values of 12.0 nM and 10 nM against A549 and K562 cells, respectively. Mechanism investigation and docking studies of 10 b indicated that it possessed good apoptosis characteristic and dose-dependent growth arrest of A549 and K562 cells, blocked cell cycle into G2/M phase. Interestingly, 10 b suppressed the growth of A549 and K562 cells via modulation of EGFR and p53-MDM2 mediated pathway.

Keywords:

• Indole derivatives
• penta-heterocycle
• anticancer
• molecular docking

Acknowledgements

The authors acknowledge the financial supports of National Natural Science Foundation of China [21867004, 22007022], Science and Technology Foundation of Guizhou Province [ZK[2021]034], Top Science and Technology Talent Program of Guizhou Education Department (2022), Guizhou Provincial Department of Education [Qjh KYZi[2021]041].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary data

¹H NMR, ¹³C NMR and HR-MS spectra for the target compounds (Figures S1−S81), ¹H NMR and ¹³C NMR spectra for t key intermediate 4(Figures S82, S83), the results of superimposition on molecular docking (Figures S84, S85) associated with this article can be found in the online version.