Synthesis and biological evaluation of piperazine group-linked bivalent β-carbolines as potential antitumor agents. Issue 12 (13th November 2015)

• Record Type: Journal Article
• Authors: Sun, Rongqin; Liu, Rui; Zhou, Chi; Ren, Zhenghua; Guo, Liang; Ma, Qin; Fan, Wenxi; Qiu, Liqin; Yu, Huijuan; Shao, Guang; Cao, Rihui
• Is Part Of: MedChemComm. Volume 6:Issue 12(2015:Dec.)
• Page Start: 2170
• Page End: 2174
• Publication Date: 2015-11-13
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c5md00312a
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : A series of bivalent β-carbolines with a piperazine group spacer between 3-methylene units were synthesized and their cytotoxic activities in vitro were evaluated. Compounds7e and7g exhibited potent cytotoxic activity. Abstract : A series of novel bivalent β-carbolines with a piperazine group spacer between 3-methylene units were synthesized and evaluated as antitumor agents. The results demonstrated that compounds7e and7g exhibited the most potent cytotoxic activities against ten tumor cell lines. Structure–activity relationships analysis indicated that (1) the substituents in positions 1 and 9 of the β-carboline ring played a significant role in modulating the antitumor activity; (2) the introduction of alkyl groups into position-9 of the β-carboline nucleus enhanced their cytotoxic potencies and the butyl substituent was the optimal group. Investigation of the preliminary mechanism of action demonstrated that compound7g showed obvious anti-angiogenic activity in the in vivo CAM assay, and the potency was similar to that of CA4P (200 μM).