Síntese e avaliação de licochalcona C (LCC) e seus análogos como potenciais agentes antibacterianos e antimicobacterianos. - Ozanique, Patrick Rombola [UNESP] (Universidade Estadual Paulista (Unesp), 2022)
O recrudescimento de bactérias e micobactérias fármaco-resistentes representam desafios à descoberta de novos agentes antibacterianos. Dessa forma, esforços são prementes para descobrir e desenvolver fármacos com padrões estruturais e mecanísticos inovadores. O presente trabalho teve como objetivo a síntese e avaliação de licochalcona C (LCC), uma chalcona C-prenilada com atividade antimicobacteriana inexplorada e atividade antibacteriana descrita como promissora. Também, serão sintetizadas duas séries de análogos chalcônicos de LCC, sendo as séries I e II com análogos modificados nos anéis A e B, respectivamente. A estratégia sintética incluiu reações de iodação e acoplamento de Suzuki, as quais permitiram regiosseletividade da C-prenilação na posição 3. A atividade antibacteriana e antimicobacteriana de LCC foi avaliada contra espécies Gram-positivas, Gram-negativas e micobactérias, exibindo valores de Concentração Inibitória Mínima de: Staphylococcus aureus MSSA (185 µM), Staphylococcus aureus MSRA (185 µM), Staphylococcus epidermidis (18 µM), Enterococcus faecalis (148 µM), Staphylococcus pneumoniae (148 µM), Streptococcus sanguinis (18 µM), Streptococcus sobrinus (37 µM), Streptococcus mutans (37 µM), Helicobacter pylori (74 µM), Pseudomonas aeruginosa (> 1.000 µM), Klebsiella pneumoniae (> 1.000 µM), Escherichia coli (> 1.000 µM), Mycobacterium tuberculosis H37Rv (92 µM), Mycobacterium kansasii (369 µM) e Mycobacterium avium (185 µM).

The resurgence of drug-resistant bacteria and mycobacteria pose challenges to the discovery of new antibacterial agents. Thus, efforts are urgent to discover and develop drugs with innovative structural and mechanistic patterns. The present work aimed at the synthesis and evaluation of licochalcone C (LCC), a C-prenylated chalcone with unexplored antimycobacterial activity and antibacterial activity described as promising. Also, two series of chalconic analogues of LCC will be synthesized, with modified analogues in rings A and B. The synthetic strategy included iodination and Suzuki coupling reactions, which allowed regioselectivity of C-prenylation at position 3. The antibacterial and antimycobacterial activity of LCC was evaluated against Gram-positive, Gram-negative and mycobacterial species, exhibiting Minimal Inhibitory Concentration values of: Staphylococcus aureus MSSA (185 µM), Staphylococcus aureus MSRA (185 µM), Staphylococcus epidermidis (18 µM), Enterococcus faecalis (148 µM), Staphylococcus pneumoniae (148 µM), Streptococcus sanguinis (18 µM), Streptococcus sobrinus (37 µM), Streptococcus mutans (37 µM), Helicobacter pylori (74 µM), Pseudomonas aeruginosa (> 1,000 µM), Klebsiella pneumoniae (> 1,000 µM), Escherichia coli (> 1000 µM), Mycobacterium tuberculosis H37Rv (92 µM), Mycobacterium kansasii (369 µM) and Mycobacterium avium (185 µM).
Synthesis and evaluation of licochalcone C (LCC) and its analogues as potential antibacterial and antimycobacterial agents.
Keywords: Licochalcona C; Iodação; Acoplamento de Suzuki; Bactérias; Micobactérias; Licochalcone C; Iodination; Suzuki coupling; Bacteria; Mycobacteria