Design, Synthesis and Evaluation of some Novel Pyrazoline Derivatives as Potential Anti-inflammatory and Antitumor Agents

Abstract

A new series of pyrazoline derivatives was designed and synthesized with the objective of developing agents with anti-inflammatory activity together with chemoprevention of hepatobiliary malignancies. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced granuloma bioassay, using celecoxib as a reference drug. Ulcerogenic effect and acute toxicity profiles (ALD50) for the most active compounds were also determined. Compound 5c was proved to display anti-inflammatory activity better than celecoxib. Compounds 4b, 5d, 5c and 8 were found to be safer than indomethacin with respect to ulcerogenic effect and were well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). Moreover, histopathological examination was carried out to detect the anti-inflammatory effect of the tested compounds on the livers of carrageenan-injected rats. On the other hand, compounds 4b, 4c, 4d, 5b, 5c, 5d, 6a, 6b, 6c, 6d, 8 and 9 were selected by the NCI to be evaluated for their anticancer activities but none has passed to the 5-dose assay. In addition, the ligand-receptor interactions of the most active compounds with COX-2 were investigated by performing docking studies using Molecular Operating Environment (MOE) version 2008.10.

Development in the Synthesis of Bioactive Thiazole-Based Heterocyclic Hybrids Utilizing Phenacyl Bromide

“…Elbayaa and coauthors 77 elucidated the synthetic pathway for the preparation of 2-(4,5-dihydro-5-(pyridin-2-yl)-3- p -tolylpyrazol-1-yl)thiazol-4(5 H )-one 53 with a satisfactory yield. The synthesis involved refluxing 1-thiocarbamoyl pyrazole derivatives 52 and phenacyl bromide 40 in ethanol for 2 h. Characterization of the resultant compounds was conducted, and their potential antiinflammatory properties were assessed using a carrageenan-induced granuloma bioassay, employing celecoxib as the standard drug for comparative analysis.…”

Synthesis and Cytotoxic Evaluation of 3-(4-Fluorophenyl)-4,5-dihydro-5-(3,4,5-trimethoxy/4-nitrophenyl)-N-(substituted-phenyl)pyrazole-1-carboxamide Analogues

“…14 All compounds I-VI contain the pyrazoline nucleus (Figure 1). Furthermore, reports of other biological activities of pyrazoline analogues include antitubercular, 15 anticonvulsant, 16 antimicrobial, 17,18 selective HER inhibition, 19 anti-inflammation, 20 anti-HIV, 17 carbonic anhydrase inhibition, 21 antiproliferatin 22,23 and tyrosinase inhibition. 14 Hence, we have synthesized some novel pyrazoline analogues and report herein their cytotoxicity evaluation.…”

“…In the initial step, (2E)-1-(4-fluorophenyl)-3-(substituted-phenyl)prop-2-en-1-one derivatives 3a and 3b were synthesized from 4-fluoroacetophenone by Claisen-Schmidt condensation. 4-Fluroacetophenone 1 (0.05 mol, 6.07 mL) and aromatic aldehyde 2a or 2b (0.05 mol) were dissolved in absolute ethanol (50 mL) and 30% NaOH solu-tion was added dropwise with continuous stirring at room temperature for 4 h. 15,19 The reaction mixture was kept standing overnight and further poured into the crushed ice to obtain a pale-yellow precipitate of (2E)-1-(4-fluorophenyl)-3-(substituted-phenyl)prop-2-en-1-one derivatives 3a and 3b. In the subsequent step an equimolar mixture of 3a or 3b and substituted phenyl semicarbazide was heated at reflux in glacial acetic acid for 12 h to obtain the 3-(4-fluorophenyl)-4,5-dihydro-5-(3,4,5-trimethoxy/4-nitrophenyl)-N-(substituted phenyl)pyrazole-1-carboxamide analogues 4a-n.…”

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“…13 3-Benzofuran-2-yl-5-(4-dimethylaminonaphthalen-1-yl)-4,5-dihydropyrazole-1-carbothioic acid amide (VI) was found to 14 All compounds I-VI contain the pyrazoline nucleus ( Figure 1). Furthermore, reports of other biological activities of pyrazoline analogues include antitubercular, 15 anticonvulsant, 16 antimicrobial, 17,18 selective HER inhibition, 19 anti-inflammation, 20 anti-HIV, 17 carbonic anhydrase inhibition, 21 antiproliferatin 22,23 and tyrosinase inhibition.…”

“…In the initial step, (2E)-1-(4-fluorophenyl)-3-(substituted-phenyl)prop-2-en-1-one derivatives 3a and 3b were synthesized from 4-fluoroacetophenone by ClaisenSchmidt condensation. 4-Fluroacetophenone 1 (0.05 mol, 6.07 mL) and aromatic aldehyde 2a or 2b (0.05 mol) were dissolved in absolute ethanol (50 mL) and 30% NaOH solution was added dropwise with continuous stirring at room temperature for 4 h. 15,19 The reaction mixture was kept standing overnight and further poured into the crushed ice to obtain a pale-yellow precipitate of (2E)-1-(4-fluorophenyl)-3-(substituted-phenyl)prop-2-en-1-one derivatives 3a and 3b. In the subsequent step an equimolar mixture of 3a or 3b and substituted phenyl semicarbazide was heated at reflux in glacial acetic acid for 12 h to obtain the 3-(4-fluorophenyl)-4,5-dihydro-5-(3,4,5-trimethoxy/4-nitrophenyl)-N-(substituted phenyl)pyrazole-1-carboxamide analogues 4a-n.…”