title: Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-c][1,2,4]triazin-6-amines.
abstract: A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 μM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 μM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Akbarzadeh
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Noushini
authors.forename: Somayeh
authors.initials: S
authors.lastname: Taban
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.forename: Mahsima
authors.initials: M
authors.lastname: Khoshneviszadeh
authors.forename: Mina
authors.initials: M
authors.lastname: Saeedi
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Mohammad
authors.initials: M
authors.lastname: Eghtedari
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Sarrafi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoshneviszadeh
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
authors.forename: Kouros
authors.initials: K
authors.lastname: Divsalar
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Moshafi
authors.forename: Ali
authors.initials: A
authors.lastname: Asadipour
authors.forename: Reyhaneh
authors.initials: R
authors.lastname: Sabourian
authors.forename: Najmeh
authors.initials: N
authors.lastname: Edraki
authors.forename: Omidreza
authors.initials: O
authors.lastname: Firouzi
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50
chemical_list: D000588:Amines