Síntese e avaliação farmacológica de novos compostos híbridos capsaicina-curcumina com potencial perfil antinociceptivo e anti- inflamatório

Abstract

In the course of time researchers have confirmed that inflammation represents a driving force associated with several chronic diseases, including obesity, diabetes, neurodegenerative disorders, etc..., in follow-up, researchers became interested in the development of more effective anti-inflammatory drugs, and specific for certain inflammatory conditions, with the ability to act on other inflammatory mediators, leading to the discovery of new drug candidates with different mechanisms of action, which could also act on multiple targets in inflammation. On the other hand, pain, which is considered as one of the 4 cardinal signs of inflammation according to the physician Aulus Cornelius Celsus, is increasing every time, becoming considered as a global problem, even though adequate treatment has not yet been reached. Thus, the present work describes 7 new hybrid capsaicin-curcumin compounds, named PQM-310 (52a), PQM-311 (52b), PQM-331 (52c), PQM-332 (52d), PQM-334 (52e), PQM-335 (52f) and PQM-336 (52g) with novel structural pattern, which were synthesized, characterized and evaluated by in silico and pharmacological studies. PQM-310 (52a), PQM-311 (52b) and PQM-332 (52d) significantly reduced the amount of leukocytes, PQM-310 (52a), PQM-311 (52b), PQM-331 (52c), PQM-332 (52d) and PQM-336 (52g) reduced the production of TNF-α. then, 2 of these compounds were screened for IL-1β count and formalin-induced paw edema assay, which were PQM-310 and PQM- 311, are considered promising candidates for prototype anti-inflammatory multi-target drugs and analgesics, potent, and not toxic. Also a study in silico of ADME properties suggested an adequate absorption profile and bioavailability of PQM-310 and PQM- 311.