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Novel quinazolin‐4(3 H )‐one linked to 1,2,3‐triazoles: Synthesis and anticancer activity
Author(s) -
Safavi Maliheh,
Ashtari Arsalan,
Khalili Faezeh,
Mirfazli Seyedeh Sara,
Saeedi Mina,
Ardestani Sussan Kabudanian,
Rashidi Ranjbar Parviz,
Barazandeh Tehrani Maliheh,
Larijani Bagher,
Mahdavi Mohammad
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13203
Subject(s) - quinazolinone , chemistry , cytotoxicity , ethidium bromide , acridine orange , erlotinib , stereochemistry , biochemistry , in vitro , apoptosis , cancer research , biology , epidermal growth factor receptor , dna , receptor
In this work, a wide range of novel quinazolin‐4(3 H )‐one linked to 1,2,3‐triazoles was designed, synthesized, and evaluated against a panel of three human breast ( MDA ‐ MB ‐231, MCF ‐7, T‐47D), lung (A549), and prostate ( PC 3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3‐triazole moieties. According to the calculated IC 50 values, compounds 6q , 6w , and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non‐small‐cell lung cancer ( NSCLC ), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g , 6u , 6w , and 6x over the EGFR active site. The most promising compounds, 6q and 6u , possessing 3‐methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction.