Open AccessSynthesis and Cytotoxic Activity of Several Novel N-Alkyl-Plinabulin Derivatives With Aryl Group Moieties
Author(s) -
Pham Thi Tham,
Duong Huong Quynh,
Nguyen Van Tuyen,
Dinh Thuy Van,
Phan Thanh Phuong,
Tran Thi Thu Hang,
Phan Văn Kiệm
Publication year - 2021
Publication title -
natural product communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.221
H-Index - 44
eISSN - 1934-578X
pISSN - 1555-9475
DOI - 10.1177/1934578x211010040
Subject(s) - piperazine , chemistry , methylene , aryl , cytotoxicity , stereochemistry , alkyl , alkylation , quinoline , benzaldehyde , medicinal chemistry , organic chemistry , in vitro , catalysis , biochemistry
Seven novel N-alkyl-plinabulin derivatives with aryl groups moieties (nitroquinoline, 1,4-dihydroquinoline, 4-methoxybenzene, and 4-chlorobenzene) have been synthesized via aldol condensation and alkylation in one-pot, and tested for their cytotoxicity against 4 cancer cell lines (KB, HepG2, Lu, and MCF7). Compounds ( Z)−3-((6,8-dimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)piperazine-2,5-dione (5a), ( Z)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)−3-((1,6,8-trimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)piperazine-2,5-dione (5b), and ( Z)−3-(( Z)−4-chlorobenzylidene)−1,4-dimethyl-6-((8-methyl-4-nitroquinolin-2-yl)methylene)piperazine-2,5-dione (8) showed strong cytotoxicity against 3 of the cancer cells lines (KB, HepG2 and Lu) with IC 50 values ranging from 3.04 to 10.62 µM. The quinoline-derived compounds had higher cytotoxic activity than the benzaldehyde derivatives. The successful synthesis of these derivatives offers useful information for the development of more potent vascular disrupting agents based on plinabulin.