Evaluation of benzothiophene carboxamides as analgesics and anti‐inflammatory agents

Abstract

Nonsteroid anti-inflammatory drugs (NSAIDs) represent standard therapy for the alleviation of pain and inflammation. At present various classes of compounds have been reported as selective inhibitors of cyclooxygenase-2 (COX-2). However, they are associated with adverse side effects. To address these issues, we report here a new class of compounds that exhibit potent analgesic and anti-inflammatory response. Substituted bromo-benzothiophene carboxamides (4-11) were examined for their analgesic and anti-inflammatory properties. Our findings demonstrate that newly synthesized bromobenzothiophene carboxamide derivatives 4, 6, and 8 attenuate nociception and inflammation at lower concentration than classical NSAIDs, such as ibuprofen. These compounds act by selectively inhibiting COX-2 and by disrupting the prostaglandin-E2-dependent positive feedback of COX-2 regulation, which was further substantiated by reduction in the levels of cytokines, chemokines, neutrophil accumulation, synthesis of prostaglandin-E2, expression of COX-2, and neutrophil activation at lower concentration than the classic NSAID ibuprofen. Toxicological study reveals that these compounds are well tolerated and metabolized to avoid any toxicity. Thus, these molecules represent a new class of analgesic and anti-inflammatory agents.

Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus

“…The development of new antibiotics targeting antibioresistant bacteria is therefore critical. Substituted benzo[ b ]thiophenes are interesting compounds in medicinal chemistry [ 5 ] that display a broad range of activity including antimicrobial [ 6 , 7 ], anticancer [ 8 ], anti-diabetic [ 9 ], anti-depressant [ 10 ], anti-inflammatory and analgesic agents [ 11 , 12 ]. As part of an ongoing research program aiming at the discovery of new potential antibiotics targeting multidrug-resistant Staphylococcus aureus strains, we combined the benzo[ b ]thiophene nucleus with the acylhydrazone functional group, which is also relevant in bioactive molecules design [ 13 ].…”

A Rapid Microwave Induced Synthesis of Isonicotinamide Derivatives and their Antifungal Activity

“…HE chemistry of carboxamide derivatives with various structural moieties have attracted much attention owing to their different biological properties: antimicrobial, [1][2][3][4][5][6] antifungal, [7][8][9][10] anti-inflammatory, [11] analgesic, [12,13] antitumoral, [14][15][16][17][18] antihypertensive, [19,20] anticonvulsant, [21,22] and antiviral [23] in the recent two decades. More than 255 of known drugs have a carboxamide group in its structure.…”