Investigation of biological activity of 2, 3-disubstituted quinazolin-4(1H)-ones against Mycobacterium tuberculosis and DNA via docking, spectroscopy and DFT studies. (14th December 2020) - Kumar, C. B. Pradeep
Abstract : Docking studies, structural data of DNA binding and molecular dynamics simulations of substituted quinazolin-4(1 H )-ones. 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.