Synthesis, Characterization, Antitubercular and Anti-Inflammatory Activity of New Pyrazolo[3,4-d]Pyrimidines.

AIMS AND OBJECTIVE: Copious proinflammatory cytokines including TNF-α and IL-1ß are involved in progression of inflammation in human body. Inhibition of signaling mediated by proinflammatory cytokines offer effective in the treatment of inflammatory diseases. The treatment of dreadful infectious disease mycobacterium tuberculosis still remains a challenge owing to resistance to multiple drugs hence an urgent need for newer drugs. Pyrazolo[3,4-d]pyrimidines have been disclosed to possess numerous pharmacological activities including anti-inflammatory, antimicrobial and antitubercular activities. Here in we report the synthesis of pyrazolo[3,4-d]pyrimidines for anti-inflammatory and antitubercular activities. MATERIALS AND METHODS: The targeted compounds having pyrazolo[3,4-d]pyrimidine scaffold 8a-m were synthesized in three step reactions with the formation of key intermediate 5-amino-4-- cyno-1-phenyl pyrazole which upon cyclization resulted in 4-amino pyrazolo[3,4-d]pyrimidine for subsequent benzoylation with substituted benzoyl chlorides to form 8a-m. Antiinflammatory activity of 8a-m was assessed at 25 mg/Kg dose and minimum inhibitory concentration against gram positive, gram negative and mycobacteria was also performed. Binding interactions were also measured in binding pocket of p38 kinase. RESULTS: Four compounds 8a, 8b, 8e and 8i significant anti-inflammatory activity in rat paw edema model induced by carrageenan and among all 8b was potent with 80.6% activity. Numerous compounds exhibited potent activity against fungal strains than bacterial strains, compound 8k was most potent against gram negative bacteria Klebsiella pneumoniae. Compounds 8d, 8e and 8f exhibited antitubercular activity with MIC value of 6.25 µg/mL. CONCLUSION: Substituted N-benzoylated amino pyrazolo[3,4-d]pyrimidines endowed significant and potent anti-inflammatory and antimicrobial activities. Molecular docking studies also revealed favorable interactions in active site of p38 kinase.

Synthesis, antibacterial, antifungal and antitubercular activities of N-pyrazolylbenzamide derivatives.

A series of new N-pyrazolylbenzamides (5a-x) were synthesized by aroylation of 5-amino-1-phenyl-3-tbutylpyrazole. The structures of synthesized compounds were established based on spectral (FTIR, (1)H NMR, ESI Mass) analysis and purity was ascertained by HPLC. The antibacterial screening revealed that seven molecules exhibited an excellent antibacterial activity and eight compounds demonstrated considerable antifungal activity. Three molecules of the series 5e, 5s and 5w were found to be highly effective against Klebsilla pneumoneia with MIC of 3.12 µg/ml. Compounds 5b, 5f, 5g and 5o exhibited significant antitubercular activity with MIC of 12.5 µg/ml.