Rajesh H. Tale

A novel pyrimidine derivatives with aryl urea, thiourea and sulfonamide moieties: synthesis, anti-inflammatory and antimicrobial evaluation.

A series of novel 4-(3-(trifluoromethyl)phenylamino-6-(4-(3-arylureiodo/arylthioureido/arylsulfonamido)-pyrimidine derivatives of biological interest were prepared by the sequential Suzuki cross coupling, acid amination, reduction followed by reaction of resulting amine with different arylisocyantes or arylisothiocyantes or arylsulfonyl chlorides. All the synthesized compounds (1-25) were screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological data revealed that among all the compounds screened, compounds 5, 6, 11, 12, 16 and 20 were found to have moderate to potent anti-inflammatory activity (up to 48-78% TNF-α and 56-96% IL-6 inhibitory activity) with reference to standard dexamethasone at 10 μM. The compounds 10, 12, 13, 18, 20, 22, 24 and 25 found to have promising antimicrobial activity against all the selected pathogenic bacteria and fungi.

Synthesis, anti-inflammatory and antimicrobial evaluation of novel 1-acetyl-3,5-diaryl-4,5-dihydro (1H) pyrazole derivatives bearing urea, thiourea and sulfonamide moieties.

A series of novel 1-acetyl-3-(3,4-dimethoxypheny)-5-(4-(3-(arylureido/arylthioureido/arylsulfonamido) phenyl)-4,5-dihydropyrazole derivatives of biological interest have been prepared by sequential cyclization of 1-(4-nitrophenyl)-3-(3,4-dimethoxyphenyl)-pro-2-ene-1 with hydrazine hydrate, reduction followed by reaction of resulting amine with different arylisocyanates or arylisothiocyanates or arylsulfonyl chlorides. All the synthesized compounds (1-32) have been screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological evaluation study showed, the compounds 4, 5, 9, 11, 14 and 16 found to have promising anti-inflammatory activity (up to 61-85% TNF-α and 76-93% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (76% TNF-α and 86% IL-6 inhibitory activity at 1 μM). Compounds 24, 26, 27, 28 and 29 exhibited promising antimicrobial activity at MIC values ranging from 70 to 10 μg/mL against all the selected pathogenic bacteria and fungi.

The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea: Synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation

A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Biginelis reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 μM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 μg/mL against selected pathogenic bacteria and fungi.

Synthesis and biological evaluation of novel piperazine derivatives of flavone as potent anti-inflammatory and antimicrobial agent

A series of novel 6-methoxy-2-(piperazin-1-yl)-4H-chromen-4-one and 5,7-dimethoxy-2-(piperazin-1-ylmethyl)-4H-chromen-4-one derivatives of biological interest were prepared and screened for their pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Among all the compound screened (5a-j and 10k-t), the compounds 5c, 5g, 5h, 10l, 10m, 10n and 10r found to have promising anti-inflammatory activity (up to 65-87% TNF-α and 70-93% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (71% TNF-a and 84% IL-6 inhibitory activities at 1 μM) while the compounds 5b, 5i, 5j, 10s and 10t found to be potent antimicrobial agent showing even 2 to 2.5-fold more potency than that of standard ciprofloxacin and miconazole at the same MIC value of 10 μg/mL.

A single, selective and simple validated method for simultaneous estimation of amiloride and hydrochlorothiazide in human plasma by liquid chromatography–tandem mass spectrometry

A single, simple and selective method for simultaneous estimation of amiloride and hydrochlorothiazide in human plasma was validated using triamterine and hydrochlorothiazide (13)C,d2 as internal standard. The compounds were separated on a reverse-phase column with an isocratic mobile phase consisting of 2 mm ammonium acetate pH 3.0 and acetonitrile (30:70, v/v) and detected by tandem mass spectrometry with positive/negative ion mode. The analytes and internal standards were extracted from plasma using simple solid phase extraction. The ion transitions recorded in multiple reaction monitoring mode were m/z 230.1 → 116.0 for amiloride, m/z 254.1 → 237.1 for internal standard, triamterine in positive mode and m/z 296.1 → 204.9 for hydrochlorothiazide, m/z 299.2 → 205.8 for internal standard, hydrochlorothiazide (13)C,d2 in negative ion mode. Linearity in plasma was observed over the concentration range 0.1-10 ng/mL for amiloride and 5.0-500.0 ng/mL for hydrochlorothiazide. The mean recovery was 41.1 and 81.5% for amiloride and hydrochlorothiazide respectively. The coefficient of variation of the assay was less than 11.2 and 5.2% for amiloride and hydrochlorothiazide, respectively, and the accuracy was 89.0-98.1 and 96.6-102.9% for amiloride and hydrochlorothiazide, respectively. The validated method can be applied to the pharmacokinetic study of amiloride and hydrochlorothiazide.

A simple, selective and rapid validated method for estimation of anastrazole in human plasma by liquid chromatography-tandem mass spectrometry and its application to bioequivalence study.

A rapid, simple and specific method for estimation of anastrazole in human plasma was validated using letrozole as internal standard. The analyte and internal standard were extracted from plasma using simple solid-phase extraction. The compound were separated on a reverse-phase column with an isocratic mobile phase consisting of 0.1% formic acid in water and acetonitrile (12 : 88, v/v) and detected by tandem mass spectrometry in positive ion mode. The ion transitions recorded in multiple reaction monitoring mode were m/z 294.1 --> 225.1 for anastrazole and m/z 286.1 --> 217.1 for internal standard. Linearity in plasma was observed over the concentration range 0.3-30 ng/mL for anastrazole. The mean recovery for anastrazole was 83.7% with a lower limit of quantification of 0.3 ng/mL. The coefficient of variation of the assay was less than 6.8% and the accuracy was 96.1-102.2%. The validated method was applied to a bioequivalence study of 1 mg anastrazole tablet in healthy human volunteers.