title: Synthesis, p38 kinase inhibitory and anti-inflammatory activity of new substituted benzimidazole derivatives.
abstract: P38 mitogen activated protein kinases have been found to involve in the production and release of unwarranted levels of pro-inflammatory cytokines including TNFα  and IL-1β  in numerous inflammatory diseases. A new series of molecules, 5-substituted benzoylamino-2-substituted phenylbezimidazoles has been synthesized from 4-nitro-1, 2- diaminobenzene. The synthesized compounds were characterized by FTIR, 1HNMR and Mass. The final compounds were screened for in vitro p38 kinase inhibitory and in vivo anti-inflammatory activity. Three compounds from the series demonstrated nearly 50% inhibition of p38 kinase in the in vitro screening method at 10  μM concentration and two molecules exhibited greater than 75% inhibition of paw oedema volume during the first hour. The docking study of synthesized molecule revealed a new binding pose in ATP binding pocket.
authors.affiliation: SVERI's College of Pharmacy, Gopalpur Road, Pandharpur- 413304, Maharashtra, India. ravigk2000@gmail.com
authors.forename: Ravindra G
authors.initials: RG
authors.lastname: Kulkarni
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Laufer
authors.forename: Chandrashekhar V
authors.initials: CV
authors.lastname: M
authors.forename: Achaiah
authors.initials: A
authors.lastname: Garlapati
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases