Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity.

Synthesis and biological evaluation of dihydroindeno and indeno [1,2-e] [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazines as antimicrobial agents.

Two series of compounds namely, dihydroindeno and indeno [1,2-e] [1,2,4]triazolo [3,4-b] [1,3,4]thiadizines (9a-l & 11a-l) were synthesized by cyclocondensation between α-bromoindanones (7a-b) or/and α,α-dibromoindanones (8a-b) and various 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3a-f) in methanol with an aim to explore their effect on in vitro growth of microorganism causing microbial infection. In vitro antibacterial activity was performed against four strains namely, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and antifungal activity against three fungal strains namely, Aspergillus niger, Aspergillus flavus, Penicillium species. Of all the compounds screened for activity some of the compounds were associated with considerably higher antibacterial and antifungal activity than commercial antibiotics.

Synthesis and biological evaluation of some 4-functionalized-pyrazoles as antimicrobial agents.

1,3-Diaryl-4-formylpyrazoles 8 bearing benzenesulfonamide moiety at position-1 were synthesized as important intermediates following Vilsmeier-Haack strategy. Aldehyde moiety of 4-formylpyrazole was then converted into carboxylic acid 9, cyano 10 and carbothioamide 11 using established procedures. Out of these 4-functionalized pyrazoles, pyrazole-4-carboxylic acids 9 and carbothioamides 11 were evaluated for their in vitro antibacterial activity against four pathogenic bacterial strains namely, Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and in vitro antifungal activity against two pathogenic fungal strains namely, Aspergillus niger and Aspergillus flavus. Three tested compounds, 9e, 11b and 11f exhibited moderate antibacterial activity against Gram-positive bacteria and 9g showed moderate antifungal activity against the tested fungi. However, none of the compounds showed any activity against Gram-negative bacteria.

A facile iodine(III)-mediated synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines via oxidation of 2-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines and their antimicrobial evaluations.

BACKGROUND: Fused heterocyclic 1,2,4-triazoles have acquired much importance because of their interesting biological properties. Although a number of methods have been reported in the literature which includes oxidation with phosphorus oxychloride, lead tetraacetate, bromine, etc., hypervalent iodine reagents have emerged as reagents of choice for various synthetically useful transformations due to their low toxicity, ready availability and ease of handling. RESULTS: A series of new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4 has been conveniently synthesized by oxidative cyclization of 2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines 3 promoted with iodobenzene diacetate under mild conditions (up to 90% isolated yields). All the new compounds were tested in vitro for their antimicrobial activity. CONCLUSIONS: Iodine(III)-mediated oxidative approach has offered an easy access to new 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines 4. The antibacterial and antifungal activities of newly synthesized compounds have proved them potent antimicrobial agents.

Synthesis of new pyrazolyl-2, 4-thiazolidinediones as antibacterial and antifungal agents.

BACKGROUND: Thiazolidine-2, 4-diones (TZDs) have become a pharmacologically important class of heterocyclic compounds since their introduction in the form of glitazones into the clinical use for the treatment of type 2 diabetes. TZDs lower the plasma glucose levels by acting as ligands for gamma peroxisome proliferators-activated receptors. In addition, this class of heterocyclic compounds possesses various other biological activities such as antihyperglycemic, antimicrobial, anti-inflammatory, anticonvulsant, insecticidal, etc. TZDs are also known for lowering the blood pressure thereby reducing the chances of heart failure and micro-albuminuria in the patients with type 2 diabetes. RESULTS: We have described herein the synthesis of three series of compounds, namely, ethyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (4), methyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (5), and 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetic acids (6). The compounds 4 and 5 were synthesized by Knoevenagel condensation between 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1) and ethyl/methyl 2-(2, 4-dioxothiazolidin-3-yl)acetates (3, 2) in alcohol using piperidine as a catalyst. The resultant compounds 4 and 5 having ester functionality were subjected to acidic hydrolysis to obtain 6. All the new compounds were tested for their in vitro antibacterial and antifungal activity. CONCLUSIONS: Knoevenagel condensation approach has offered an easy access to new compounds 4-6. Antimicrobial evaluation of the compounds has shown that some of the compounds are associated with remarkable antifungal activity. In case of antibacterial activity, these were found to be effective against Gram-positive bacteria. However, none of the compounds were found to be effective against Gram-negative bacteria.

Synthesis and antimicrobial evaluation of new 1,4-dihydro-4-pyrazolylpyridines and 4-pyrazolylpyridines.

BACKGROUND: Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHP) have now been recognized as vital drugs. Some of these derivatives such as amlodipine, felodipine, isradipine, etc. have been commercialized. In view of wide range of biological properties associated with 1,4-DHP and owing to the biological importance of the oxidation step of 1,4-DHP, we carried out the synthesis and antimicrobial evaluation of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) and diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g). RESULTS: Synthesis of a series of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) has been accomplished by multicomponent cyclocondensation reaction of ethyl acetoacetate, 3-aryl-1-phenyl pyrazole-4-carboxaldehyde (1a-g) and ammonium acetate. The dihydropyridines 2a-g were smoothly converted to new diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g) using HTIB ([Hydroxy (tosyloxy)iodo]benzene, Koser's reagent) as the oxidizing agent. The antimicrobial studies of the title compounds, 2a-g &3a-g, are also described.

Synthesis and biological evaluation of some pyrazolylpyrazolines as anti-inflammatory-antimicrobial agents.

A new series of pyrazolylpyrazolines (5a-k) was synthesized by the reaction of appropriate chalcones (3a-k) with 4-hydrazinobenzenesulfonamide hydrochloride (4) in ethanol. All the newly synthesized target compounds (5a-k) were screened for their anti-inflammatory activity using carrageenan-induced rat paw edema assay. Compounds 5g and 5j showed pronounced anti-inflammatory activity comparable to the reference standard nimesulide, whereas, compounds 5b, 5d and 5h displayed good anti-inflammatory activity. Additionally, the synthesized compounds were evaluated for their in vitro antimicrobial activity against two Gram-positive bacteria and two Gram-negative bacteria. Four compounds 5c, 5h-5j showed good broad spectrum activity against all the tested Gram-positive and Gram-negative bacterial strains. Compound 5j could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory and antibacterial profile.

Organoiodine (III) mediated synthesis of 3-aryl/hetryl-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidines as antibacterial agents.

Synthesis of some new 3-aryl/hetryl-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidines (3a-k) has been accomplished by the oxidation of 4,6-dimethyl-2-pyrimidinylhydrazones of various aldehydes with iodobenzene diacetate in dichloromethane. Nine new compounds (3b-g and 3i-k) were tested in vitro for their antibacterial activity. Two compounds, namely 3-(4'-pyridyl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine (3k) and 3-(3',4'-dimethoxyphenyl)-5,7-dimethyl-1,2,4-triazolo[4,3-a]pyrimidine (3f), were associated with substantially higher antibacterial activity than some commercial antibiotics against Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Salmonella typhi at MIC (minimum inhibitory concentration) i.e. 10 microg/ml.

Hypervalent iodine mediated synthesis of 1-aryl/hetryl-1,2,4-triazolo[4,3-a] pyridines and 1-aryl/hetryl 5-methyl-1,2,4-triazolo[4,3-a]quinolines as antibacterial agents.

Oxidation of 2-pyridyl and 2-quinylhydrazones with iodobenzene diacetate (IBD) in dichloromethane yield 1-aryl/hetryl-1,2,4-trizolo-[4,3-a] pyridines (3a-f) and 1-aryl/hetryl-5-methyl-1,2,4-triazolo[4,3-a] quinolines (6a-f). Seven compounds were tested in vitro for their antibacterial activity. 1-(5'-Nitro-2-furyl)-5-methyl-1,2,4-triazolo[4,3-a]quinoline (6e) was associated with substantially higher antibacterial activity than some commercial antibiotics against Salmonella typhi at MIC i.e. 10 microg mL(-1).