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Design, Synthesis and Bioevaluation of Two Series of 3‐[(1‐Benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3 H )‐ones and N ‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines
Author(s) -
Lan Ta Thu,
Anh Duong Tien,
PhamThe Hai,
Dung Do Thi Mai,
Park Eun Jae,
Jang Sun Dong,
Kwon Joo Hee,
Kang Jong Soon,
Thuan Nguyen Thi,
Han SangBae,
Nam NguyenHai
Publication year - 2020
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202000290
Subject(s) - chemistry , cytotoxicity , stereochemistry , docking (animal) , acetylcholinesterase , aché , triazole , enzyme , in vitro , biochemistry , organic chemistry , medicine , nursing
Two series of 3‐[(1‐benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3 H )‐ones and N ‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N ‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N ‐(1‐Benzylpiperidin‐4‐yl)quinazolin‐4‐amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC‐3 (prostate cancer), and NCI−H23 (lung cancer), with 3‐[(1‐benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3 H )‐one being the most cytotoxic agent. 3‐[(1‐Benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3 H )‐one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N ‐(1‐benzylpiperidin‐4‐yl)quinazolin‐4‐amines could serve as new leads for further design and AChE inhibitors, while 3‐[(1‐benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methyl]quinazolin‐4(3 H )‐one could serve as a new lead for the design and development of more potent anticancer agents.