Design, Synthesis and Biological Activity Evaluation of β-Carboline Derivatives Containing Nitrogen Heterocycles

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 21; p. 5155
• Main Authors: Wu, Guiyun, Wang, Wenhang, Li, Fulian, Xu, Chenlu, Zhou, Yue, Li, Zhurui, Liu, Bingqian, Shao, Lihui, Chen, Danping, Bai, Song, Wang, Zhenchao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2024; MDPI
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; antitumor; Apoptosis; Apoptosis - drug effects; Biological activity; Cancer therapies; Carbolines - chemical synthesis; Carbolines - chemistry; Carbolines - pharmacology; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cyclin-dependent kinases; Drug Design; Drug development; Drug Screening Assays, Antitumor; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Kinases; Molecular Structure; Motility; Natural products; Nitrogen; Nitrogen - chemistry; PC-3 Cells; Phase transitions; Raltegravir; Reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; Structure-Activity Relationship; β-carboline derivatives; apoptosis; antitumor; cell cycle; β-carboline derivatives; ROS
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29215155

A series of β-carboline derivatives containing nitrogen heterocycles were designed and synthesized. All compounds were screened for their antitumor activity against four human tumor cell lines (A549, K562, PC-3, T47D). Notably, compound N-(4-(morpholinomethyl)phenyl)-2-((5-(1-(3,4,5-trimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl)-1,3,4-oxadiazol-2-yl)thio)acetamide (8q) exhibited significant inhibitory activity against PC-3 cells with an IC50 value of 9.86 µM. Importantly, compound 8q effectively suppressed both the proliferation and migration of PC-3 cells. Mechanistic studies revealed that compound 8q induced cell apoptosis and caused the accumulation of reactive oxygen species (ROS), leading to cell cycle arrest in the G0/G1 phase in PC-3 cells.