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New series of arylazo-pyrazoles and arylazopyrazolo[1,5-a]pyrimidines are designed, synthesized, and evaluated for antimicrobial activity. The structures of new compounds were supported by IR, 1H N...

Antimicrobial chemotherapy is the clinical application of antimicrobial agents to treat infectious disease. A new series of 3,6-disubstituted- and 2,3,6-trisubstitutedquinoxalines have been synthes...

A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4–7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Compound 12d exhibited potent sub-micromolar activity against HepG-2 and MCF-7 (IC50 = 0.07 and 0.08 μM, respectively). In-silico pharmacophore modelling of this chemotype compounds disclosed a five features' pharmacophore model representing essential steric and electronic fingerprints essential for activity. Finally, a 2D-QSAR model was devised to quantitatively correlate the 2D molecular feature descriptors of this series of thiobarbiturates with their cytotoxic activity against MCF-7. Finally, in silico evaluation of the physicochemical and ADME properties of these derivatives was performed.

Novel pyrrolo[2,3-d]pyrimidines 5a–j, 6a–j and pyrrolo[2,3-b]pyridines 7a–h; incorporating the common vicinal diaryl motif of tumor necrosis factor-α (TNF-α) inhibitors, were synthesized starting from 2-amino-pyrrole-3-carbonitriles 1a–h. The structures of synthesized compounds were elucidated by spectral data (IR, NMR, and MS) and elemental analyses. Representative compounds were evaluated for their ability to inhibit lipopolysaccharide-induced TNF-α production in vivo in rat at 25 mg/kg p.o. Structure activity relationships are described. The pyrrolo[2,3-d]pyrimidines displayed better inhibitory activity than the pyrrolo[2,3-b]pyridines. The most potent among the biologically tested compounds was the pyrrolopyrimidine 5h (N-(4-ethoxyphenyl)-2-(4-oxo-6-phenyl-7-(pyridine-4-yl)-4H-pyrrolo[2,3-d]pyrimidin-3(7H)-yl)acetamide),showing TNF-α inhibitory activity (96 %) comparable to that of dexamethasone (91 %).

(Z)-1-amino-4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-imidazol“5(4H)”one 2 was synthesized from the corresponding oxazolone 1. Condensation with different phenacyl bromide derivatives yielded our target compounds 4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-1-(2-oxophenyl/substitutedphenylethylamino)-1H-imidazol“5(4H)”one 3a–f. On the other hand, oxazolone 1 was allowed to react with dl-alanine to obtain (Z)-2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)propanoic acid 4. Chlorination followed by reaction with appropriate aromatic amines gave our compounds 2-(4-(2,4-difluorobenzylidene)-2-(4-fluorophenyl)-5-oxo-4,5-dihydroimidazol-1-yl)-N-phenyl/substitutedphenylpropanamide 6a–c. All the target compounds were evaluated for their anticonvulsant activity using mean electroshock (MES) test at an oral dose of 100 mg/Kg. Most of the compounds showed protection against seizures with a potency ranging from 70 to 96%. However, compounds 3d, 6b, and c showed excellent protection against seizures with a potency of 92.84, 96.42, 96.42%, respectively, with respect to the reference standard phenytoin with a potency of 100%. To assess the locomotor coordination and neurological deficit, animals were tested on the rotarod, the most promising compounds did not affect the stability of mice on rotarod at the same dose level.

5,12-Dihydrobenzophenazine-6,11-diones,2-Arylamino-3-chloro-1,4-naphthoquinones and 6,11-dihydrobenzo[b]phenazine-6,11-diones, were synthesized from 2,3-dichloro-1,4-naphthoquinoneand arylamines/phenylenediamines. Studying thecytotoxicity using EAC and human cell lines revealed that 5,12-dihydrobenzo[b]phenazine-6,11-dione (3) and 3-chloro-2-(2-pyridylamino)-1,4-naphthoquinone (10) showed selectivecytotoxicity against the human lung carcinoma cell line (H460)superior to doxorubicin. Compound 3 (16.25 uM) was 1.3 timeshigher than that of doxorubicin. However, IC50 value of compound10 was 9.90 uM which was 2 times higher than that (20.10 uM) ofdoxorubicin. These compounds were inactive against livercarcinoma (HEPG2), brain tumor (U251), cervix carcinoma(HELA) and breast carcinoma (MCF7) cell lines.

We synthesized 2-(4-(4-fluorobenzylidene)-2-(4-fluorophenyl) 5-oxo-4,5-dihydroimidazol-1-yl) acetic acid 3. Chlorination afforded the chloro derivative 4, which reacted with different amines and hydrazine to afford compounds 5-8. Pyrazole, pyrazolone, and thiazolidinone derivatives were also synthesized from Imidazol-1-ylacetic acid hydrazide 8 to give compounds 9-12. Compounds were then evaluated for their anti-inflammatory activity against carrageenan-induced rat paw edema and their analgesic activity using the writhing test in albino mice. Compounds 5, 9, 10, 12 exhibited maximum anti-inflammatory activity, and all the compounds inhibited writhing, with 10 and 12 being two times more effective than the reference standard.

A series of new pyrrole derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrrolotriazolopyrimidines and pyrrolotetrazolopyrimidines were synthesized. The evaluation of their antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans were carried out. Pyrrolo[2,3-d]pyrimidines 3a-d, 7a,e, 11d exhibited excellent activity against C. albicans with MIC 0.31-0.62 mg/mL. These compounds displayed better antifungal activity than that of standard drug (fluconazole with MIC 1.5 mg/mL). Furthermore, pyrrolo[2,3-d]pyrimidines 3b,c, 7e exhibited the best activity against S. aureus with MIC 0.31 mg/mL, compared with the standard drug (ampicillin with MIC 0.62 mg/mL). The rest of the compounds were found to be inactive against bacteria and fungi.

Three novel series of 2-(substituted phenyl)-4-(substituted arylidene)-imidazolone-5-(4H)-ones were derived from the corresponding oxazolones by condensation with different arylamines. Eleven of the synthesized compounds were selected and evaluated for their effect on carrageenan-induced rat paw edema. Compound 4b had the same efficacy as the reference standard (indomethacin), and compounds 3b, 3c, 4a, 4d and 9a showed good to excellent activities, with other compounds only weakly active. The potent compounds were evaluated for their inhibitory activities against COX-2-catalyzed PGE(2) production, with 4a, 4b and 3c showing strong inhibitory activity.

In this study twenty six novel derivatives of 6-oxo-pyridine-3-carboxamide were synthesized and evaluated as antibacterial and antifungal agents. Synthesis of the 2-amino-4-methyl-6-oxo-N,1-diphenyl-1,6-dihydropyridine-3-carboxamide 1 was carried out by reacting equimolar quantities of acetoacetanilide and cyanoacetanilide in ethanol using triethylamine as a catalyst. The results of the in vitro antimicrobial evaluation showed that, the 6-oxo-N,1-diphenyl-5-(p-tolyldiazenyl)-1,6-dihydropyridine-3-carboxamide, 5c displayed broad-spectrum antibacterial activity which was equipotent to both Ampicillin and Gentamicin against the tested bacteria. Moreover, compounds 3a, 5c and 9b were equipotent to the reference drug, Amphotericin B, against Aspergillus fumigatus (MIC = 1.95µg/ml). 2D QSAR studies were carried out in order to correlate the observed activity to the binding mode of these compounds, in addition to their molecular properties that might be controlling their activities.