title: 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 bromo-benzothiophene 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. © 2014 IUBMB Life, 66(3):201-211, 2014.
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Chandramani
authors.initials: C
authors.lastname: Pathak
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Ranjan Singh
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.|Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Kapoor
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Varshiesh
authors.initials: V
authors.lastname: Raina
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
authors.forename: Sarika
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Molecular Sciences Lab, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.|Molecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka, India.
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
keywords: COX-2; anti-inflammatory; anti-nociceptive; bromo-benzothiophene caroboxamide derivatives; hyperalgesia