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Design, synthesis and evaluation of multi-pharmacophore-containing spiropolycyclic harmaline-based hybrids as anticancer agents.

Authors :
Chen, Shuang
Yu, Ze-Hua
Wang, Wei-Na
Chen, Zi-Yue
Pan, Bo-Wen
Chen, Lin
Zhou, Ying
Liu, Xiong-Wei
Liu, Xiong-Li
Source :
New Journal of Chemistry. 4/7/2023, Vol. 47 Issue 13, p6073-6085. 13p.
Publication Year :
2023

Abstract

Here, we demonstrate the first example of natural product harmaline and its derivatives serving as useful N–C synthons in formal [3+2] cycloadditions with isothiocyanates for the construction of a library of spiropolycyclic harmaline-based hybrids containing two adjacent quaternary stereocentres. These products were smoothly afforded in up to 90% yield, 20 : 1 dr with Et3N as the catalyst under mild conditions. To the best of our knowledge, this also represents the first example of the synthesis of natural product harmaline-based spiropolycyclic scaffolds, and expands the chemical space of biologically significant harmaline derivative species. The newly synthesized structurally diverse compounds were evaluated for their in vitro anticancer activities. These studies indicate that some compounds displayed good anticancer activity against three tumor cells (A549, K562, and PC-3). Among them, compound 3cb displayed the best activity when applied to A549, which is similar to that of cisplatin. Preliminary mechanistic studies indicate that compound 3cb induces apoptosis in A549 cells through a caspase-dependent pathway. These results show that compound 3cb can be prepared as a good lead for drug development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
11440546
Volume :
47
Issue :
13
Database :
Academic Search Index
Journal :
New Journal of Chemistry
Publication Type :
Academic Journal
Accession number :
162733079
Full Text :
https://doi.org/10.1039/d2nj05987h