DFT theoretical calculations on (Z)-2-hydroxy-N′-(4-oxo-1,3-thiazolidin-2-ylidene) benzohydrazide as a methylene tetrahydrofolatereductase inhibitor: An in silico study, molecular docking, and molecular dynamics simulations

In this study, (Z)-2-hydroxy-N′-(4-oxo-1,3-thiazolidin-2-ylidene)benzohydrazide (HTBH) was theoretically studied. The B3LYP/6-311G (d,p) level of calculation was used to accomplish the optimal molecular geometry, the global reactivity descriptor parameters, Fukui functions, and molecular electrostatic potential (MEP) parameters. The reduced density gradient (RDG) was used to explore the non-covalent interactions in the molecular system. Furthermore, possible nonlinear optical characteristics were explored. These properties include the electric dipole moment, mean polarizability, and first and second hyperpolarizabilities, indicating the intriguing uses of the HTBH in optical systems. The dipole moment of HTBH molecule was calculated to be 6.81 D, while the static second order hyperpolarizabilitywas found to be of 29.86×10-36esu. In addition, the MEP map provides insight into the electrostatic potential distribution within the molecule indicating that most nucleophilicand electrophilic regions are around oxygen atoms and H atom of the hydroxyl group, respectively.Using molecular docking, the inhibitory nature of HTBH against the methylene tetrahydrofolatereductase (NADPH) protein was analyzed. This enzyme involves in folate metabolism, and its inhibition can have implications for various biological processes. Finally, through a detailed molecular dynamics (MD) simulation, we unravel the compound's inhibitory potential and binding characteristics, offering valuable information for developing therapeutic interventions. The binding energies were computed as well by using the MM-PBSA.