Synthesis and evaluation of the antinociceptive effects of some newly designed compounds containing sulfonamide moieties

In this thesis, 10 novel compounds containing sulfonamide moieties were designed, synthesized, and their potential antinociceptive activities were investigated using in vivo methods. The possible interactions of these compounds with cyclooxygenase (COX) enzymes were also examined through in silico approaches. The data obtained from the hot plate and tail clip tests conducted to investigate antinociceptive effects demonstrated that the 10 mg/kg doses of the compounds in the series did not prolong the response times in mice. These findings suggest that the compounds do not exhibit antinociceptive effects at the spinal or supraspinal level in models of acute thermal or mechanical nociceptive pain. In contrast, compounds coded 4a, 4b, 4d, 4f, 4g, 4i, and 4j significantly reduced the nociceptive responses of mice to chemically-induced pain stimuli in the acetic acid-induced writhing test and the early phase of the formalin test. These results indicate that the compounds are effective in tonic pain models associated with peripheral inflammatory processes. Molecular docking studies conducted to provide insight into the potential mechanisms of action revealed that compound 4j interacts with COX-1, whereas compounds 4f, 4g, and 4i interact with the COX-2 enzyme. The stability of the complex formed between compound 4i and the active site of COX-2 was further confirmed through molecular dynamics simulations. While this study contributes novel sulfonamide derivatives with antinociceptive properties to the literature, further comprehensive pharmacokinetic (e.g., bioavailability, half-life, tissue distribution) and pharmacodynamic (e.g., efficacy, safety) investigations are required to evaluate the drug-likeness and therapeutic potential of the effective compounds.