Synthesis and Biological Assessment of Carbazole Linked Pyrazole Schiff bases and Diarylthiourea Derivatives (original) (raw)
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Amino-5-(3-fluoro-4-methoxyphenyl)thiophene-3-carbonitrile have been synthesized from 1-(3-fluoro-4methoxyphenyl)ethanone, malononitrile, a mild base and sulfur powder using Gewald synthesis technique and the intermediate was treated with 1,3-disubstituted pyrazole-4-carboxaldehyde to obtain the novel Schiff bases. 1,3-disubstituted pyrazole-4-carboxaldehyde derivatives have been synthesized by Vilsmeier-Haack reaction in the course of a multi-step reaction. The structure of novel compounds were established on the basis of their elemental analyses IR, 1 H NMR, 13 C NMR, and mass spectral data and then screened for their in vitro antimicrobial activity. Among them 5a, 5c, 5f and 5h showed excellent activity when compared to other derivatives. Remaining derivatives showed moderate activity.
European Journal of Medicinal Chemistry, 2018
New 1,3,4-trisubstituted pyrazole derivatives were synthesized and evaluated for their antiplasmodial activity. Compounds 4b, 4c, 7a and 7d were the most potent antiplasmodial agents against P. berghei with percent of suppression ranging from 90-100 %. They were also screened for their in vitro antimalarial activity against the chloroquine resistant strain P. falciparum, (RKL9). Compound 4c displayed the highest in vitro antimalarial activity; 13-fold higher than standard chloroquine phosphate. Molecular docking of the most active compounds against the wildtype and quadruple mutant pf DHFR-TS structures rationalized the in vitro antimalarial activity. Furthermore, these compounds exhibited reasonable in silico druglikeness and pharmacokinetic properties. Toxicity studies of the most active compounds revealed that all tested compounds were non-toxic and well-tolerated up to 150 mg/kg via oral route and 75 mg/kg via parentral route. According to RBC hemolysis assay, it was found that compound 7a was the most potent anti-inflammatory and least toxic derivative with IC 50 value 71-fold higher than IC 50 value related to the antimalarial activity. Moreover, cytotoxicity assessment revealed that compound 4c was the least toxic derivative with IC 50 value 70000fold higher than IC 50 value related to the antimalarial activity.
Synthesis, characterization and antibacterial activity of some new pyrazole based Schiff bases
Arabian Journal of Chemistry, 2013
In the present study a series of new Schiff bases were synthesized. All the synthesized compounds were characterized by IR, 1 H NMR, mass spectral and elemental analyses. Newly synthesized compounds were screened for their antibacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) activity. The results revealed that, compounds 3f and 3c have exhibited significant biological activity against the tested microorganisms.
A series of 3,5-disubstituted pyrazole-1-carbothioamides 2a-d, 4a-d, 5a-d and pyrimidine-2(1H)-thiones 6a-d were prepared by cyclocondensation of chalcones 1a-d with either thiosemicarbazide or thiourea, respectively. Dehydrative cyclization of chalcones 1a-d with thiosemicarbazide in refluxing dioxane containing few drops of acetic acid gave the corresponding 4,5-dihydropyrazoles 2a-d which were subsequently oxidized with sodium hypochlorite in dioxane to give pyrazole-1-carbothioamides 4a-d. N-acetyl derivatives of pyrazole-1-carbothioamides were obtained by two routes. Treat-ment of either hydrazones 3a-d or pyrazole-1-carbothioamides 4a-d with acetic anhydride gave the desired N-acetyl deriva-tives of pyrazole-1-carbothioamides 5a-d. Finally, cyclocondensation of chalcones 1a-d with thiourea in ethanolic potas-sium hydroxide gave the corresponding pyrimidine-2-(1H)-thiones 6a-d. The structural identification of products is re-ported and also the heterocyclic compounds were scree...
Discovery of novel pyrazoles as potent antimicrobial and antimalarial agents
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Some 1-aryl-3-alkyl-4-substituted aryl (or heteroaryl)-5 amino pyrazole derivatives have been synthesized by the reaction of substituted aryl or hetero aryl acetonitrile with alkyl acetate( ethyl acetate or ethyl trifluoroacetate ) followed by reaction with phosphorous oxychloroide and further by cyclisation with substituted aryl hydrazine in presence of triethyl amine in ethanol . All the synthesized compounds were characterized by elemental analysis, 1H NMR and LCMS. These were screened for in-vitro antimicrobial activity against two gram positive (Streptococcus pyogenes and Staphylococcus aureus ) and two gram negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) along with antifungal and antimalarial activity.
Journal of enzyme inhibition and medicinal chemistry, 2015
Two series of 1-substituted carbamoyl and thiocarbomoyl derivatives were prepared by either treating the corresponding pyrazole with the appropriate isocyanate and isothiocyanate respectively, or alternatively by condensing the appropriate diketone with the proper substituted semicarbazide or thiosemicarbazide. The structures of the prepared compounds were fully determined by analytical and spectral methods. Preliminary biological screening of the prepared compounds revealed significant antibacterial and cytotoxic activities for some compounds. Compounds 4a2 and 4a3 were found to be the most active against the human colon carcinoma HT29 (11.8 and 7.5 μg/mL, respectively) and human breast cancer MCF 7 (3.4 and 2.6 μg/mL, respectively) cell lines. The structure-activity relationship (SAR) and in silico drug relevant properties (HBD, HBA, tPSA, cLog P, molecular weight, % ABS, drug-likeness and drug score) further confirmed that the compounds are potential lead compounds for future dru...
Acta Pharmaceutica, 2015
Triphenylimidazol-2-yl-thio)butyric acid hydrazide (3) was obtained via alkylation of 1,4,5-triphenylimidazol-2thiol (1) with ethylbromobutyrate, followed by addition of hydrazine hydrate. Treatment of acid hydrazide 3 with carbon disulfi de in an ethanolic potassium hydroxide solution gave the intermediate potassium dithiocarbazinate salt, which was cyclized to 4-amino-5-[(1,4,5-triphenylimidazol-2-yl)thiopropyl]-2H-1,2,4-triazole-3-thione (4) in the presence of hydrazine hydrate. Condensation of compound 3 with alkyl/arylisothiocyanate aff orded the corresponding 1-[4-(1,4,5-triphenylimidazol-2-ylthio)butanoyl]-4-alkyl/arylthiosemicarbazides (5-7), which upon refl uxing with sodium hydroxide, yielded the corresponding 1,2,4-triazole-3-thiols 8-10. Under acidic conditions, compounds 4-6 were converted to aminothiadiazoles 11-13. Moreover, the series of Schiff bases 14-18 were synthesized from the condensation of compound 3 with diff erent aromatic aldehydes. The newly synthesized compounds were characterized by IR, 1 H NMR, 13 C NMR and mass spectral analyses. They were also preliminarily screened for their antimicrobial activity.
A series of tetrasubstituted pyrazole-3-carboxamides (3a–c) and pyr-azole-3-carbonyl thioureides (6a–c) were synthesized and their structures characterized by IR, NMR and elemental analysis. The antibacterial potential against specific Gram-positive and Gram-negative strains and the antifungal activities of all novel compounds were investigated. Structure–activity relationships (SAR) studies and some theoretical parameters (ClogP, CMR, PSA and ESP) of the compounds were performed on these two pyrazole derivatives. Pyrazole-3-carboxylate ester 2 was used for the synthesis of the carboxamide derivatives. The reactions of pyrazole-3-carbonyl isothiocyanate 5 with appropriate chiral amino alcohols were utilized for synthesizing the thioureide derivatives. Both of these types of pyrazole derivatives including a chiral moiety exhibited pronounced antibacterial activities. According to the present in vitro study, some of the promising compounds might be new candidates for a new generation of antibacterial drugs.