Síntese e avaliação de análogos de 3-Hidroxicordoína como potenciais agentes contra Mycobacterium tuberculosis
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Data
2023-04-28
Autores
Carvalho, Maria Isabel Gomes de
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Universidade Estadual Paulista (Unesp)
Resumo
A tuberculose (TB) é uma doença infecciosa causada pela bactéria Mycobacterium tuberculosis (MTB). Atualmente, essa doença é considerada um problema de saúde pública devido ao alto número de casos. Inúmeras razões justificam a busca por novos agentes tuberculostáticos, destacando-se a sua alta taxa de morbimortalidade. Dessa maneira, esforços são prementes para descobrir e desenvolver fármacos com padrões estruturais e mecanísticos inovadores. A Química Medicinal tem sido muito importante para esta busca, visando o planejamento e a descoberta de fármacos. As chalconas vêm se destacando por possuírem inúmeras bioatividades e sua síntese ser considerada concisa e versátil. O presente estudo teve como objetivo a síntese e avaliação biológica de 3-hidroxicordoína (3HC) e seus análogos. Foram sintetizados análogos chalcônicos com modificações no anel A e a estratégia sintética incluiu reações de O-alquilação, condensação aldólica de Claisen-Schmidt, rearranjo de Claisen e hidrogenação catalítica.. A atividade antibacteriana da 3HC foi avaliada contra Mycobacterium tuberculosis H37Rv obtendo uma Concentração Inibitória Mínina (CIM) de 3,9 µM.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). Currently, this disease is considered a public health problem due to the high number of cases. Numerous reasons justify the search for new tuberculostatic agents, highlighting their high morbidity and mortality rate. Therefore, efforts are urgent to discover and develop drugs with innovative structural and mechanistic patterns. Medicinal Chemistry has been very important for this search, aiming at the planning and discovery of drugs. Chalcones have been highlighted because they have numerous bioactivities and their synthesis is considered concise and versatile. The present study aimed at the synthesis and biological evaluation of 3-hydroxychordoin (3HC) and its analogues. Chalconic analogues with modifications in the A ring were synthesized and the synthetic strategy included O-alkylation reactions, Claisen-Schmidt aldol condensation, Claisen rearrangement and catalytic hydrogenation. The antibacterial activity of 3HC was evaluated against Mycobacterium tuberculosis H37Rv obtaining an Inhibitory Concentration Minimum (MIC) of 3.9 µM.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). Currently, this disease is considered a public health problem due to the high number of cases. Numerous reasons justify the search for new tuberculostatic agents, highlighting their high morbidity and mortality rate. Therefore, efforts are urgent to discover and develop drugs with innovative structural and mechanistic patterns. Medicinal Chemistry has been very important for this search, aiming at the planning and discovery of drugs. Chalcones have been highlighted because they have numerous bioactivities and their synthesis is considered concise and versatile. The present study aimed at the synthesis and biological evaluation of 3-hydroxychordoin (3HC) and its analogues. Chalconic analogues with modifications in the A ring were synthesized and the synthetic strategy included O-alkylation reactions, Claisen-Schmidt aldol condensation, Claisen rearrangement and catalytic hydrogenation. The antibacterial activity of 3HC was evaluated against Mycobacterium tuberculosis H37Rv obtaining an Inhibitory Concentration Minimum (MIC) of 3.9 µM.
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Palavras-chave
Cordoína, Chalconas preniladas, Claisen-Schmidt, Tuberculose, Bactérias, Cordoin, Prenylated chalcones, Tuberculosis, Bacteria