Muhammad Tariq Khan, Humaira Nadeem, Ahmed Sadiq Sheikh, Nadia Shamshad Malik, Muhammad Rizwan, Muhammad Imran, Ibrahim Javed, Muhammad Usman Munir, Arif Ullah Khan, Akash Syed, Muzaffar Abbas.
Amino acid derivatives of 2-Mercaptobenzimidazoles suppress cytokines at the site of inflammation and block gastric H+/K+ ATPase..
Pak J Pharm Sci Jan ;34(3):1157-63.

Routinely used anti-inflammatory drugs are associated with off-target effects such as cyclooxygenase (COX)-1 inhibition and gastric ulcers. The aim of this study is to examine the anti-inflammatory potential and gastroprotective effects of synthetic amino acid derivatives of 2-mercaptobenzimidazole (MBAA1, MBAA2, MBAA3, MBAA4 and MBAA5). The results showed that compound MBAA5 possess a potential anti-inflammatory action by inhibition of 15-LOX and COX-2. MBAA5 also attenuated the pro-inflammatory cytokines and mediators (TNF-α, IL-1β and COX-2) in rat hind paw in carrageenan-induced inflammatory model of rat. 2-mercaptobenzimidazole derivative, MBAA5 also inhibited gastric H+/K+ ATPase and demonstrated a better selectivity index for COX-2 (SI 27.17) in comparison to celecoxib (SI 41.43). Molecular docking studies predicted the binding interactions of the synthesized compounds with retrieved target proteins of H/K ATPase, COX-1, COX-2, and 15-LOX. The results of in silico and molecular docking analysis of amino acid derivatives of 2-mercaptobenzimidazoles further explained their pharmacological activities. Moreover, these compounds presented better antimicrobial activity against three clinical isolates of Helicobacter pylori. Together, our findings suggested that these synthetic 2-mercaptobenzimidazole derivatives are safer therapeutic candidates for inflammation.

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