ABSTRACT
Abstract Over time, the effective resistance mechanisms to various first- and second-line drugs against the disease of tuberculosis make its treatment extremely difficult. This work presents a new approach to synthesizing a hybrid of antituberculosis medications: isoniazid (INH) and pyrazinamide (PZA). The synthesis was performed using ultrasound-assisted synthesis to obtain an overall yield of 70%, minimizing the reaction time from 7 to 1 h. The evaluation of the biological activity of the hybrid (compound 2) was tested using the tetrazolium microplate assay (TEMA), showing inhibition in the growth of Mycobacterium tuberculosis H37Rv at a concentration of 0.025 mM at pH 6.0 and 6.7.
Resumen Debido a los grandes mecanismos de resistencia a lo largo del tiempo de diversos fármacos de primera y segunda línea contra la enfermedad de la tuberculosis, el tratamiento sigue dificultándose. Este trabajo presenta un nuevo enfoque para sintetizar un híbrido de fármacos antituberculosos: isoniazida (INH) y pirazinamida (PZA). La síntesis fue asistida por ultrasonido con el fin de obtener un rendimiento global del 70%, minimizando el tiempo de reacción de 7 a ' h. La evaluación de la actividad biológica del híbrido (compuesto 2) se probó usando el ensayo de microplaca de tetrazolio (TEMA), que mostró una inhibición en el crecimiento de Mycobacterium tuberculosis H37Rv a una concentración de 0,025 mM a pH 6,0 y 6,7.
Resumo Devido aos grandes mecanismos de resistência ao longo do tempo a diversos fármacos de primeira e segunda linha contra a tuberculose, o que torna seu tratamento extremamente difícil. Este trabalho apresenta uma nova abordagem para sintetizar um híbrido de fármacos antituberculose: isoniazida (INH) e pirazinamida (PZA) A síntese foi realizada utilizando a síntese assistida por ultrassom de forma a obter um rendimento global de 70%, minimizando o tempo de reação de 7 h para ' h. A avaliação da atividade biológica do híbrido (composto 2) foi testada utilizando o ensaio de microplaca de tetrazólio (TEMA), mostrando uma inibição no crescimento de Mycobacterium tuberculosis H37Rv na concentração de 0,025 mM em pH 6,0 e 6,7.
ABSTRACT
AIM: Phytomedicine has been commonly practiced as a form of traditional medicine in various cultures for the treatment of oral diseases. Recently, it has gained importance as an alternative to conventional treatment. Several extracts of plants and fruits have been recently evaluated for their potential activity against microorganisms involved in the development of dental caries. The purpose of this study was to evaluate the antimicrobial activity and antiadherent effect of the crude organic extract (COE) and three partitions (aqueous, butanolic, and chloroformic) of Psidium guajava (guava) leaves on a cariogenic biofilm model. MATERIALS AND METHODS: Guava leaves were obtained from the mountains of northern Peru, where they grow wild and free of pesticides. The antimicrobial activity of the COEs and partitions against Streptococcus mutans and Streptococcus gordonii was determined by measuring the inhibition halos, while the effect on biofilm adhesion was determined by measuring the optical density using spectrophotometry. RESULTS: An antibacterial effect of the COE and chloroformic partition against S. gordonii (p < 0.05) was found, as was a significant effect on biofilm adherence, with a minimum inhibitory concentration (MIC) of 0.78 mg/mL, which was maintained throughout the 7 days of evaluation. CONCLUSION: We conclude that the COEs and their chloroformic partition have antimicrobial and antibiotic effects against this strain of S. gordonii, making them of particular interest for evaluation as a promising alternative for the prevention of dental caries. CLINICAL SIGNIFICANCE: By knowing the antimicrobial effect of Psidium guajava, this substance can be effectively used in products aimed to prevent dental caries and periodontal disease.
Subject(s)
Anti-Infective Agents/pharmacology , Dental Caries/drug therapy , Psidium , Biofilms , Humans , Peru , Plant LeavesABSTRACT
Theoretical and experimental studies on the energetic, structural and some other relevant physicochemical properties of the antioxidant tyrosol (1), hydroxytyrosol (1OH) molecules and the corresponding radicals 1rad⢠and 1Orad⢠are reported in this work. The experimental values of the gas-phase enthalpy of formation, Δf Hm0(g), in kJ·mol-1, of 1 (-302.4 ± 3.4) and 1OH (-486.3 ± 4.1) have been determined. Quantum chemical calculations, at DFT (M05-2X) and composite ab initio G3 and G4 levels of theory, provided results that served to (i) confirm the excellent consistency of the experimental measurements performed, (ii) establish that the stabilizing effect of H-bond of hydroxyethyl chain and aromatic ring (OH···π interaction) is smaller in radicals than in parent molecules, (iii) deduce-combining experimental data in isodesmic reactions-Δf Hm0(g) of radicals 1rad⢠(-152.3 ± 4.4 kJ·mol-1) and 1Orad⢠(-370.6 ± 3.8 kJ·mol-1), (iv) estimate a reliable O-H bond dissociation enthalpy, BDE of 1 (368.1 ± 5.6 kJ·mol-1) and of 1OH (333.7 ± 5.6 kJ·mol-1), and (v) corroborate-using "BDE criteria"-than 1OH is a more effective antioxidant than 1.
