Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles.

Two series of compounds namely, 4-aryl/heteroaryl hydrazino-3-acetyl-6-methyl-2H-pyran-2-ones (4a-4j) and pyrano[4,3-c]pyrazoles (6a-6e and 6g) were synthesized starting from 3-acetyl-4-chloro-6-methyl-2H-pyran-2-one (2). Estimation of pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side effects and interaction with drug-metabolizing enzymes were made for the synthesized compounds on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by PharmaExpert software. COX inhibition predicted by PASS was confirmed by experimental evaluation and validated via docking studies. Out of all the compounds, compounds 4h, 4j, 6e, 6g exhibited good anti-inflammatory activity, whereas compounds 4b, 4c, 4h, 4i, 4j, 6b, 6e, 6g showed excellent analgesic activity compared with standard drug Diclofenac sodium.

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 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.