title: Synthesis and Evaluation of New 4-Chloro-2-(3-chloro-4-fluorophenyl)-5-(aliphatic/cyclic saturated amino)pyridazin-3(2H)-one Derivatives as Anticancer, Antiangiogenic, and Antioxidant Agents.
abstract: 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(2H)-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.
authors.affiliation: Organic Chemistry Research Laboratory, Department of Chemistry, Institute of Science, Nagpur, Maharashtra, India.
authors.forename: Vinod T
authors.initials: VT
authors.lastname: Kamble
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Sawant
authors.forename: Sanjay S
authors.initials: SS
authors.lastname: Sawant
authors.forename: Parshuram M
authors.initials: PM
authors.lastname: Pisal
authors.forename: Rajesh N
authors.initials: RN
authors.lastname: Gacche
authors.forename: Sonali S
authors.initials: SS
authors.lastname: Kamble
authors.forename: Vilas A
authors.initials: VA
authors.lastname: Kamble
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010851:Picrates / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D000975:Antioxidants; D001713:Biphenyl Compounds; D010851:Picrates; D011728:Pyridones; D013481:Superoxides; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Antiangiogenic; Anticancer; Antioxidant activity; Pyridazinones