Synthesis, Antimicrobial Activity, and Molecular Modeling Studies of Some Benzoxazole Derivatives

Abstract

Background: The need for the development of novel antimicrobial agents is apparent as infectious diseases are increasing and resistance is rapidly developing against the drugs used in the treatment. Objective: This study aimed at the synthesis, antimicrobial susceptibility testing, and computational elucidation of the mechanism of action of benzoxazole derivatives. It also aimed at comparing the results obtained in this study with the previous studies by our group. This would pave the way for designing novel molecules with better antimicrobial activity. The other goal was pharmacophore analysis and in silico ADMET analysis of them. Methods: In this study, synthesis, antimicrobial susceptibility testing, molecular docking, pharmacophore analysis, and ADMET prediction were carried out. Results: The antimicrobial activity studies demonstrated that the synthesized compounds were active against standard strains and clinical isolates at high concentrations. Then, the antimicrobial testing results were compared to similar benzoxazoles tested by our group previously. Benzoxazole derivatives without methylene bridge between oxazole and phenyl ring were found to be more active than those with the methylene bridge. This was also confirmed by molecular modeling undertaken in this study. The computational results indicated that the antibacterial activity could be achieved by DNA gyrase inhibition. Pharmacophore analysis showed that hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), and hydrophobicity features would contribute to the inhibition. In addition, in silico ADMET property investigation of the compounds exhibited that they had the desired pharmacokinetics. Conclusion: Although antibacterial activity by inhibiting DNA gyrase is selective, the synthesized compounds were active at much higher concentrations than the standards. Therefore, in prospective antimicrobial studies, it is better to focus on benzoxazole derivatives without the methylene bridge. Since the compounds had suitable in silico ADMET properties, screening them against the other pharmacologic activities should be carried out. It is recommended to support the molecular modeling results with in vitro or in vivo studies.

Synthesis, DFT Calculations, and Molecular Docking Study of Acetohydrazide‐Based Sulfonamide Derivatives as Paraoxonase 1 Inhibitors

“…The filtrate was acidified with concentrated HCl acid, and the precipitate was filtered off and dried. The dried solid was crystallized with water [58,59] . Yield 82 % M. P.: 140–141 °C, CAS # 59‐49‐4.…”

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine‐class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity

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“…MD simulations were undertaken through GROMACS (GROningen MAchine for Chemical Simulations) package. 30 The topology of the compounds was generated through PRODRG server. 31 The force field used in the MD simulation was CHARMM.…”

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