Title:Synthesis, Antimicrobial Activity, and Molecular Modeling Studies of
Some Benzoxazole Derivatives
Volume: 19
Issue: 8
Author(s): Muhammed Tilahun Muhammed*, Gulcan Kuyucuklu, Fatma Kaynak-Onurdag and Esin Aki-Yalcin
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey
- Department of Basic Biotechnology, Institute of Biotechnology, Ankara University, Ankara, Turkey
Keywords:
ADMET, antimicrobial, benzoxazole, drug design, molecular docking, pharmacophore.
Abstract:
Background: The need to develop 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 to compare 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
a 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.