Synthesis <i>N</i>-Phenyl Pyrazoline from Dibenzalacetone and Heme Polymeration Inhibitory Activity (HPIA) Assay

Abstract

The synthesis of 1,5-diphenyl-3-styryl-4,5-dihydro-1H-pyrazole (B1) and 5-(3,4-dimethoxyphenyl)-3-(3,4-dimethoxystyryl)-1-phenyl-4,5-dihydro-1H-pyrazole (B2) have been conducted from 1,5-diphenylpenta-1,4-dien-3-on (A1) and 1,5-bis(3,4-dimethoxyphenyl)penta-1,4-dien-3-one (A2). Heme polymerization inhibitory activity (HPIA) assay of the synthesized compounds has also been carried out. The first step of reaction was Claisen-Schmidt condensation of benzaldehyde derivatives and acetone using NaOH 20% and ethanol as solvent. Dibenzalacetone derivatives were reacted with phenylhydrazine using acetic acid to form N-phenylpyrazoline. The structure of products was characterized by FT-IR, GC-MS, DI-MS, 1H- and 13C-NMR The result of heme polymerization inhibitory activity assay showed that IC50 of B1 and B2 1.26 and 0.79 mM while quinine 1.26 mM. The result indicated that compound B2 was more potent as antimalarial than quinine.

Molecular Docking, Synthesis and <i>In Vitro</i> Antiplasmodium Assay of Monoketone Curcumin Analogous from 2-Chlorobenzaldehyde

“…Compound 3 was prepared using the procedure as in the previous report [11] with slight modifications. The 2chlorobenzaldehyde (0.45 mL, 4 mmol) and cyclohexanone (0.21 mL, 2 mmol) were dissolved in ethanol (10 mL).…”

“…According to Table 3, the molecular weight of the analogous 3, 4, and 6 ranged from 343.25 to 434.36 g/mol, the amount of HBA ranged from 1 to 2, the amount of HBD ranged from 0 to 1 and the log P value ranged from 4.33 to 5.66. While the curcumin analogue 4 met the Lipinski Rules of Five, the analogues 3 and 4 violated one parameter of log P. Chander et al [31] also stated that 95% of clinically approved drugs had the following range of physicochemical properties: molecular weight (130-725), HA (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), HD (0-6) and log P (−2 to 6.5). Therefore, all the analogous 3, 4, and 6 met the physicochemical properties as stated in the previous study [31].…”

“…They also demonstrated that introducing a chloro substituent at the ortho position could improve the antimalarial activity against chloroquine-sensitive (3D7) and chloroquineresistant (RKL9) strains of P. falciparum and could give a low resistance index. Previous studies also reported that coupling 2-chlorobenzaldehyde with various ketones such as N-methyl-4-piperidone, 4-piperidone, and cyclohexanone could generate bioactive curcumin analogous with anticancer, antibacterial and antiparasitic activities, respectively [9][10][11].…”