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Synthesis and Evaluation of New 4‐Chloro‐2‐(3‐chloro‐4‐fluorophenyl)‐5‐(aliphatic/cyclic saturated amino)pyridazin‐3(2 H )‐one Derivatives as Anticancer, Antiangiogenic, and Antioxidant Agents
Author(s) -
Kamble Vinod T.,
Sawant Ajay S.,
Sawant Sanjay S.,
Pisal Parshuram M.,
Gacche Rajesh N.,
Kamble Sonali S.,
Kamble Vilas A.
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400442
Subject(s) - chemistry , antioxidant , dpph , stereochemistry , ascorbic acid , bromide , hydrazine (antidepressant) , biological activity , biochemistry , in vitro , organic chemistry , food science
Pyridazinones are widely recognized as versatile scaffolds with a wide spectrum of biological activities. In the present work, a series of new 4‐chloro‐2‐(3‐chloro‐4‐fluorophenyl)‐5‐(aliphatic/cyclic saturated amino)pyridazin‐3(2 H )‐one derivatives 4a – i were synthesized and characterized by spectral techniques. The inhibitory effects of the synthesized compounds 4a – i on the viability of three human cancer cell lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60 (leukemia), were assessed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 4a – i screened, 4g and 4i exhibited inhibitory activity very close to the standard methotrexate; therefore, these lead compounds were further tested for their potential to inhibit the proangiogenic cytokines involved in tumor progression. Compound 4g was found to be a potent antiangiogenic agent against TNFα, VEGF, FGFb, and TGFβ, whereas 4i showed potent antiangiogenic activity against TNFα, VEGF, FGFb, and leptin. All the compounds 4a – i were screened for their antioxidant activities using 2,2‐diphenyl‐1‐picryl hydrazine (DPPH), OH, and superoxide anion radicals. Compound 4f showed better OH radical scavenging activity than the standard ascorbic acid.