Synthesis and antitumor activities of 4-(1H-indol-1-yl)-4-oxobutanoic acid spliced podophyllotoxin derivatives

• Published in: Synthetic communications Vol. 53; no. 3; pp. 262 - 273
• Main Authors: Yang, Jun, Liang, Guang-Ping, Liu, Xiong-Li
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis 01.02.2023; Taylor & Francis Ltd
• Subjects: Anticancer properties; antitumor activity; Apoptosis; Chemistry; Chemistry, Organic; Colchicine; derivatives; Hydrogen bonds; Lead compounds; Molecular docking; Physical Sciences; Podophyllotoxin; Science & Technology; Selectivity; derivatives; ETOPOSIDE; DESIGN; Podophyllotoxin; antitumor activity
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2023.2164863

To investigate the effects and mechanisms of 4-(1H-indol-1-yl)-4-oxobutanoic acid spliced podophyllotoxin derivatives (3a-3l) on tumor cells. The MTT method was adopted to evaluate (3a-3l) antitumor activity in vitro against A549 cells, A549/DDP cells, MCF-7 cells. The results showed that compound 3l had the most prominent inhibitory effect and high selectivity with IC 50 18.53 ± 1.51 µM against A549/DDP cells. Meanwhile, the effects of compound 3l on the nuclear state, cell cycle and apoptosis of A549/DDP cells showed that compound 3l induced apoptosis by delaying the G 2 /M phase of A549/DDP cell cycle. In addition, molecular docking of compound 3l also showed that it could form a good hydrogen bond with ARG-158 (d = 2.6, 2.7 Å) and HIS-406 (d = 2.5 Å) at the colchicine site of tubulin. Compound 3l could provide lead compound for the development of new multi-drug resistant anti-tumor drugs.