Design, synthesis and evaluation of mutual prodrug of 4-biphenylacetic acid and quercetin tetramethyl ether (BPA-QTME) as gastrosparing NSAID.
A novel mutual prodrug consisting of 4-biphenylacetic acid (BPA) and quercetin tetramethyl ether (QTME) has been synthesized as a gastrosparing NSAID, devoid of ulcerogenic side effects. The physicochemical properties, including aqueous solubility, partition coefficient, chemical stability and enzymatic hydrolysis of synthesized derivative have been studied to assess its prodrug potential. Its antiinflammatory, antiulcer and analgesic activities were also evaluated. The results indicated that BPA-QTME derivative is chemically stable, biolabile and possesses optimum lipophilicity. The synthesized compound also exhibited retention of antiinflammatory activity with reduced ulcerogenicity. Based on these observations, the therapeutic potential of this mutual prodrug is discussed.
University Institute of Pharmaceutical Sciences, Panjab University, Sector-14, Chandigarh 160014, India.
Mamta
M
Madhukar
Shruti
S
Sawraj
Pritam Dev
PD
Sharma
D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D004487:Edema / Q000188:drug therapy; D004798:Enzymes / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D051379:Mice; D010648:Phenylacetates / Q000009:adverse effects* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs; D011794:Quercetin / Q000009:adverse effects* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012995:Solubility; D014456:Ulcer / Q000139:chemically induced
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004798:Enzymes; D010648:Phenylacetates; D011355:Prodrugs; C012776:biphenylylacetic acid; D011794:Quercetin