Title:Substituted Benzamides from Anti-inflammatory and p38 Kinase Inhibitors to Antitubercular Activity: Design, Synthesis and Screening
Volume: 18
Issue: 17
Author(s): Ravindra Kulkarni*, Umakant Mitkari, G. Achaiah*, Stefan Laufer, D.V.R.N. Bikshapti, V.M. Chandrashekar, P.B. Gurav, S.J. Joshi and V.D. Chipade
Affiliation:
- SVERI`s College of Pharmacy, Gopalpur Road, Pandharpur-413 304, Maharashtra State,India
- University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh,India
Keywords:
Anti-inflammatory, antimicrobial, antitubercular, benzamide, p38 kinase, edema.
Abstract: Background: Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl
groups have been synthesized by benzoylation of respective amines in presence of base with moderate
to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory,
anti-inflammatory, antimicrobial and antitubercular activities.
Method: Anti-inflammatory activity was determined using carrageenan induced rat paw edema model
while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was
employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity
at 10 µM and best anti-inflammatory activity was found for compounds 4g, 4i, 4n and 4o which
exhibited to reduce paw edema over 70%. Compound 4b was observed to be the most potent against
gram +ve organisms with MIC value of 1.6 µG/mL and compound 4u displayed potent antibacterial
activity against gram negative organisms.
Conclusion: Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with
6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations
of compounds was performed. These preliminary results will certainly show fruitful directions to
improve the activities of compounds.
