Abstract
A series of 2,3-disubstituted quinazolin-4(1
H
)-ones (
3a-j
) were screened for their antimicrobial activity
via
the minimum inhibitory concentration method (MIC). The
in vitro
anti-tubercular (TB) activity of compounds against
Mycobacterium tuberculosis
(Mtb) H37Rv was evaluated. Among the screened compounds,
3g
and
3h
exhibited more potent anti-TB activity with MIC values of 2.15 and 0.75 μM, respectively. The compound
3g
and
3h
were tested for cytotoxic activity against the mammalian Vero cell line. Docking studies were performed on the enoyl acyl carrier protein (InhA) to understand the mechanism of actions of the compounds. The study revealed that the compounds have a strong anti-TB activity and showed a good affinity toward the protein. Hence, the target compounds
3g
and
3h
can be adapted and produced more effectively as lead compounds in the treatment of multi-drug resistant tuberculosis. Furthermore, the interaction of lead compounds
3g
and
3h
with DNA was studied by UV-Visible, fluorescence, and circular dichroism (CD) spectroscopy, cyclic voltammetry (CV) and dynamic viscosity measurements. The studies showed that the groove binding mode of interaction is predominant between DNA and compounds (
3g
and
3h
). The viscosity and absorption results obtained for compound
3g
indicated that the Ct-DNA binding properties were enhanced as compared to compound
3h
with
K
b
values of 8.58 × 10
4
and 3.41 × 10
4
L Mol
−1
, respectively. The B3LYP level of density functional theory (DFT) was used to obtain ground state geometries, molecular electrostatic potential (MEP) surfaces, and HOMO-LUMO energy calculations.
Docking studies, structural data of DNA binding and molecular dynamics simulations of substituted quinazolin-4(1
H
)-ones.