RESUMEN

Two new developments of antibacterial agents, a series of benzofuran-triazine based compounds (8a-8h) were designed and synthesized. The derivatives were prepared through conventional chemical reactions and structurally characterized with FT-IR, 1H and 13C NMR techniques. The antibacterial activity of the synthesized derivatives was assessed against gram-positive bacterial strains (Bacillus subtilis, and Staphylococcus aureus) and gram-negative bacterial strains (Salmonella entritidis and Escherichia coli). Compound 8e, with the MIC value of 125-32 µg/µl against all the examined strains of bacteria, was the most active antibacterial compound. The synthesized derivatives were also studied for docking to the binding sites of dihydrofolate reductase (DHFR) receptor which has a key role in drug resistance associated with bacterial infections. The synthesized compounds showed good interaction with the targets through hydrogen bonding and hydrophobic interactions. According to antibacterial and docking studies, compound 8e could be introduced as a candidate for development of antibacterial compounds.

RESUMEN

To design and develop novel antimicrobial agents, a series of phthalimide-triazine-based derivatives (6a-6e) were synthesized, characterized and evaluated for their potential antibacterial activities. The compounds were prepared through reaction of 6-phenyl-1,3,5-triazine-2,4-diamine with phthalimide moiety containing aliphatic amino acid. Structural analysis of the synthesized compounds was carried out by various characterization techniques such as FT-IR, 1H and 13C-NMR and mass spectroscopy. After the confirmation of the structure, the antibacterial screening of the synthesized compounds was performed against two strains of Gram-positive (Staphylococcus aureus, and Bacillus subtilis) and two strains of Gram-negative (Escherichia coli and Salmonella enteritidis) bacteria. The results of antimicrobial activity showed that compound 6d was the most active against all the tested strains of microorganisms with the MIC value 1.25 µg/µl. The synthesized compounds were docked into the binding sites of E. coli-DNA gyrase B and S. aureus-DNA gyrase complex to explore their theoretically binding mode and possible interactions of these ligands with these two targets. Docking study showed the importance of both hydrogen bonding and hydrophobic interactions as a key interaction with the targets. Based on the obtained results, the hybrid derivatives of triazine and phthalimide could be regarded as efficient candidates for further molecular developments of antimicrobial agents.

Asunto(s)

Girasa de ADN , Escherichia coli , Simulación del Acoplamiento Molecular , Girasa de ADN/metabolismo , Escherichia coli/metabolismo , Staphylococcus aureus , Espectroscopía Infrarroja por Transformada de Fourier , Antibacterianos/farmacología , Antibacterianos/química , Ftalimidas/farmacología , Aminoácidos , Triazinas/farmacología , Triazinas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad

RESUMEN

Background and purpose: Layered double hydroxides (LDHs) as inorganic materials are being used in controlled release and drug delivery systems. These materials are more stable than conventional drug carriers. In this investigation, Mg/Al-ascorbic acid (ASA) LDH nanohybrid was synthesized by ultrasonic-assisted co-deposition techniques. Experimental approach: In this study, Mg/Al-LDH to adsorption of ASA anions from the alkaline solution was assembled by a facile coprecipitation technique. During this process, ultrasonic irradiation was used to increase the rate of ion exchange between LDH and ASA. The intercalated-layered structure was characterized by FT-IR spectroscopy, XRD, thermogravimetric analysis, field emission SEM, and TEM. ASA releasing from Mg/Al-ASA LDH nanohybrid was carried out in incubation sodium carbonate solution (0.5 M) at 35 °C using UV-Vis absorbance analysis at λ = 265 nm. Findings/Results: The used techniques confirmed the structure of Mg/Al-LDH and indicated successful intercalation of ASA into the interlayer galleries of the LDH host. The obtained results also have shown that Mg/Al-ASA LDH nanohybrid was generated with an average diameter size of 25 nm and narrow size distribution. Analysis of the release profiles using several kinetic models suggested that the first-order rate model is the most appropriate for describing the release of ASA from Mg/Al-LDH which means the amount of drug released is proportional to the amount of remaining drug in the matrix. Thus, the amount of activity released tends to decrease in function of time. Conclusion and implications: The results showed that LDHs are good host materials to preserve the biomolecule and modify its release rate and bioavailability.