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.

Novel hydroxycinnamamide from morpholine and pyrrolidine: Synthesis, characterization, docking study, and anticancer activity against P388 leukemia murine cells

“…For the second target compound, hydroxycinnamoil moiety was combined with a heterocyclic amine, pyrrolidine. Other chemical constituents bearing morpholine and pyrrolidine moieties, such as tetrazole (Łukowska-Chojnacka et al, 2019), pyridazinone (Kamble et al, 2017), pyrazolidine (Surendra Kumar et al, 2017), and kojic acid derivatives (Karakaya et al, 2019), have been obtained and have showed moderate-to-high biological activities, such as antifungal, antioxidant, antimicrobial, cytotoxic, and tyrosinase inhibitory activities.…”

Chloroxylon swietenia (Roxb.) DC induces cell death and apoptosis by down‐regulating the NF‐κB pathway in MCF‐7 breast cancer cells: In vitro and in vivo investigations

“…In vitro MTT testing was done in accordance with the standard method mentioned earlier to determine CSLME's effect on breast cancer cells. 21 Inoculation of the MCF‐7 cells at 1 × 10 5 cells/ml density was carried out in 96 well culture plates. The cells were treated with different CSLME concentrations dissolved in 0.1% DMSO (Thermo Fisher Scientific, #D12345), and incubated for 48 h. The 20 μl MTT (2 mg/ml; ThermoFisher Scientific, #M6494), was applied to each well after the incubation time and the cells were incubated further at 37°C for 4 h. Further, formazan crystals were dissolved in isopropanol and the amount of formazan produced was estimated at 570 nm.…”

“…In vitro MTT testing was done in accordance with the standard method mentioned earlier to determine CSLME's effect on breast cancer cells 21 . Inoculation of the MCF‐7 cells at 1 × 10 5 cells/ml density was carried out in 96 well culture plates.…”

Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents

“…A number of pyridazinone analogs have been reported as anticonvulsant lead compounds . Apart from antiepileptic activity of pyridazinone nucleus, other activity includes antidepressant , antihypertensive , antithrombotic , cardiotonic , anti‐inflammatory , antimicrobial , anticancer , antioxidant , antiviral , diuretics, etc. .…”