Aims and Objective: Copious proinflammatory cytokines including TNF-α and IL-1β
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.