Background: Quinazolines and quinazolinones derivatives are well known for their
important range of therapeutic activities.
Objective: The study aims to carry out the synthesis of some derivatives of substituted
fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal,
and anti-biofilm activities.
Method: Compounds were chemically synthesized by conventional methods. Structures were established
on the basis of spectral and elemental analyses. The antimicrobial potential was tested
against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as
anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational
studies were performed using Auto dock free software package (version 4.0) to explain the predicted
mode of binding.
Result: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant
antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had
a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant
MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good
MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards
S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives
with their receptor-site and detected their predicted mode of binding.
Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm
activities. Modeling study explained their binding mode and showed strong binding affinity
with their receptor-site. The highly active compounds 5 and 10c could be subjected to future
optimization and investigation to be effective antimicrobial agents.