Palavras-chave
Derivado pirazólico
Atividade antimicrobiana
CIM
Como Citar
Copyright © | Todos os direitos reservados.
A revista detém os direitos autorais exclusivos de publicação deste artigo nos termos da lei 9610/98.
Reprodução parcial
É livre o uso de partes do texto, figuras e questionário do artigo, sendo obrigatória a citação dos autores e revista.
Reprodução total
É expressamente proibida, devendo ser autorizada pela revista.
Resumo
Objetivo: Analisar a atividade antimicrobiana de uma chalcona tiofênica e de um derivado pirazólico sintetizados por meio de rotas químicas específicas. Métodos: Trata-se de um estudo experimental in vitro. A chalcona tiofênica (GA-01) foi sintetizada por condensação aldólica e seu derivado pirazólico (GA-04) por ciclocondensação com tiossemicarbazida. A caracterização dos compostos foi realizada por RMN de ¹H e ¹³C. Avaliou-se a atividade antimicrobiana por meio da determinação da concentração inibitória mínima (CIM) frente a Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus e Candida albicans, utilizando o método de microdiluição em placa. Para investigar o mecanismo de ação, foi realizado um ensaio com sorbitol a 0,8 M, avaliando-se o impacto osmoprotetor na eficácia dos compostos. Resultados: A chalcona GA-01 apresentou CIM de 128 μg/mL para todas as linhagens. Já GA-04 mostrou maior atividade, com CIM de 64 μg/mL para as bactérias e 4 μg/mL para C. albicans. No ensaio com sorbitol, observou-se aumento das CIMs para ambas as substâncias, sugerindo atuação sobre a parede celular microbiana. Conclusão: As substâncias sintetizadas apresentaram potencial antimicrobiano promissor, com destaque para o derivado pirazólico (GA-04) inédito, que demonstrou maior eficácia. Os resultados apontam esses compostos como protótipos para o desenvolvimento de novos agentes antimicrobianos.
Referências
ANSARI A, et al. Review: biologically active pyrazole derivatives. New journal of chemistry, 2017; 41(1): 16–41.
ARDIANSAH, B. Chalcones bearing N, O, and S-heterocycles: Recent notes on their biological significances. Journal of applied pharmaceutical science, 2019; 9(8): 117–129.
BERTOLDO JB, et al. Synthetic compounds from an in house library as inhibitors of falcipain-2 from Plasmodium falciparum. Journal of enzyme inhibition and medicinal chemistry, 2015; 30(2): 299–307.
BHAT MA, et al. Synthesis, anti-inflammatory and neuroprotective activity of pyrazole and pyrazolo[3,4-d]pyridazine bearing 3,4,5-trimethoxyphenyl. Medicinal chemistry research: an international journal for rapid communications on design and mechanisms of action of biologically active agents, 2017; 26(7): 1557–1566.
BORCHHARDT DM, et al. Biochemical evaluation of a series of synthetic chalcone and hydrazide derivatives as novel inhibitors of cruzain from Trypanosoma cruzi. Journal of the Brazilian Chemical Society, 2010; 21(1):142–150.
BOULEBD H. The role of benzylic-allylic hydrogen atoms on the antiradical activity of prenylated natural chalcones: a thermodynamic and kinetic study. Journal of biomolecular structure & dynamics, 2021; 39(6): 1955–1964.
CANO A, et al. State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections. Journal of nanobiotechnology, 2020; 18(1).
CHIARADIA LD, et al. Synthesis, biological evaluation, and molecular modeling of chalcone derivatives as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases (PtpA and PtpB). Journal of medicinal chemistry, 2012; 55(1): 390–402.
DUARTE GD. Preparação e avaliação de atividade antimicrobiana de chalconasheterocíclicas. Dissertação de Mestrado - Universidade Federal da Paraíba, JoãoPessoa,2020; 87p.
FERREIRA NC, et al. Anti-prion activity of a panel of aromatic chemical compounds: In vitro and in silico approaches. PloS one, 2014; 9(1): e84531.
GOMES M, et al. Chalcone derivatives: Promising starting points for drug design. Molecules (Basel, Switzerland), 2017; 22(8): 1210.
HASSAN GS, et al. New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES. European journal of medicinal chemistry, 2019; 171(1): 332–342.
HASSAN MM, FAROUK O. Synthesis and antimicrobial evaluation of some functionalized heterocycles derived from novel quinolinyl chalcone. Journal of heterocyclic chemistry, 2017; 54(6): 3133–3142.
HELMY YA, et al. Antimicrobial resistance and recent alternatives to antibiotics for the control of bacterial pathogens with an emphasis on foodborne pathogens. Antibiotics (Basel, Switzerland), 2023; 12(2): 274.
HORLEY NJ, et al. (E)-3-(3,4,5-Trimethoxyphenyl)-1-(pyridin-4-yl)prop-2-en-1-one, a heterocyclic chalcone is a potent and selective CYP1A1 inhibitor and cancer chemopreventive agent. Bioorganic & medicinal chemistry letters, 2017; 27(24): 5409–5414.
INSUASTY B, et al. Synthesis of 1‐substituted 3‐aryl‐5‐aryl(hetaryl)‐2‐pyrazolines and study of their antitumor activity. Archiv der Pharmazie, 2012; 345(4): 275–286.
JORDA A, ZEITLINGER M. Preclinical pharmacokinetic/pharmacodynamic studies and clinical trials in the drug development process of EMA-approved antibacterial agents: A review. Clinical pharmacokinetics, 2020; 59(9): 1071–1084.
KHAN SA, et al. Microwave assisted synthesis of chalcone and its polycyclic heterocyclic analogues as promising antibacterial agents: In vitro, in silico and DFT studies. Journal of molecular structure, 2019; 1190(1): 77–85.
KRISHNAMURTHIVR, et al. A new analysis method for evaluating bacterial growth with microplate readers. PloS one, 2021; 16(1): e0245205.
LAGU SB, et al. Design, synthesis, and antibacterial and antifungal activities of novel trifluoromethyl and trifluoromethoxy substituted chalcone derivatives. Pharmaceuticals (Basel, Switzerland), 2020; 13(11): 375.
LAL K, et al. Design, synthesis, characterization, antimicrobial evaluation and molecular modeling studies of some dehydroacetic acid-chalcone-1,2,3-triazole hybrids. Bioorganic chemistry, 2018; 77(1): 236–244.
MACHADO C. et al. Heterocyclic chalcone derivatives: Synthesis and biological activity evaluation: PS207. Porto biomedical journal, 2017; 2(5): 225.
MAO Z. et al. Concise synthesis and biological evaluation of chalcone derivatives bearing n-heterocyclic moieties. Heterocycles, 2019; 92(6).
OLIVEIRA JWA, et al. Bactérias gram-negativas multirresistentes: revisão sobre os desafios e demais discussões. Caderno de Publicações Univag, 2021; 0(11).
PAN T, et al. Biotoxicity and bioavailability of hydrophobic organic compounds solubilized in nonionic surfactant micelle phase and cloud point system. Environmental science and pollution research international, 2017; 24(17): 14795–14801.
PRABHUDEVA MG, et al. Amberlyst-15 catalyzed synthesis of novel thiophene–pyrazoline derivatives: spectral and crystallographic characterization and anti-inflammatory and antimicrobial evaluation. Research on chemical intermediates, 2018; 44(11): 6453–6468.
ROA BM, et al. Avaliação do uso da resazurina em teste de suscetibilidade in vitro frente a Sporothrix brasiliensis. VITTALLE - Revista de Ciências da Saúde, 2019; 31(2): 32–37.
SAYED GH, et al. Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications. Journal of molecular liquids, 2018; 252(1): 329–338.
SHANKARAIAH N, et al. Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors. Bioorganic & medicinal chemistry, 2017; 25(17): 4805–4816.
TAKATE SJ, et al. Thiazolyl-pyrazole derivatives as potential antimycobacterial agents. Bioorganic & medicinal chemistry letters, 2019; 29(10): 1199–1202.
TANG X, et al. Novel chalcone derivatives containing a 1,2,4-triazine moiety: design, synthesis, antibacterial and antiviral activities. RSC advances, 2019; 9(11): 6011–6020.
VANANGAMUDI G, et al. Synthesis, spectral linearity, antimicrobial, antioxidant and insect antifeedant activities of some 2,5-dimethyl-3-thienyl chalcones. Arabian journal of chemistry, 2017; 10(1): S1254–S1266.
XUE Y. et al. Antiradical activity and mechanism of coumarin–chalcone hybrids: Theoretical insights. The journal of physical chemistry. A, 2018; 122(43): 8520–8529.
ZHAO C, et al. Nitrogen-doped carbon quantum dots as an antimicrobial agent against Staphylococcus for the treatment of infected wounds. Colloids and surfaces. B, Biointerfaces, 2019; 179(1): 17–27.
ŻYSZKA B, et al. Highly effective, regiospecific reduction of chalcone by cyanobacteria leads to the formation of dihydrochalcone: two steps towards natural sweetness. Microbial cell factories, 2017; 16(1).