DFT calculations and molecular docking studies on benzazol-2-carboxamide derivatives

The newly synthesized benzazole-2-carboxamide type molecules (N-(benzo[d]thiazole-2-yl)benzamide, N-(benzo[d]thiazole-2-yl)-4-chlorobenzamide, N-(1H-benzo[d]imidazole-2-yl)benzamide, N-(benzo[d]oxazole-2-yl)benzamide, N-(1H-benzo [d]imidazole-2-yl)benzamide, N-(1H-benzo [d]imidazole-2 -il)-4-chlorobenzamide, N-(benzo[d]oxazole-2-yl)-4-chlorobenzamide, N-(benzo[d]thiazole-2-yl)-4-methylbenzamide, N-(1H-benzo[d]imidazole-2-yl)-4-methylbenzamide, N-(benzo[d]oxazole-2-yl)-4-methylbenzamide) experimental and mechanical quantum by performing comparative analyses of the results obtained from their calculations, The aim was to obtain new drug candidate molecules with a performance comparable to the potential strong and selective cytotoxic effects of similar structures that have been previously studied against cancer cells. X-ray diffraction (XRD) patterns of the compounds were collected with an X-ray diffractometer using Cu Kα radiation (λ = 1.5406 Å, 45 mV and 40 mA). Optimization processes of the compounds were carried out using the Gaussian 09W package program and the GaussView 5.0 interface program. In the calculations, the molecules were assumed to be in the gas phase and DFT/B3LYP theory/functionals and the 6-311++G(d,p) basis set were used. Vibrational calculations of the compounds were made, and the VEDA4 program (Potential Energy Distribution) was used to increase the accuracy of the vibrational assignments. To obtain FT-IR spectra of the compounds, a Perkin Elmer 400 (USA) FTIR/FIR Spectrometer Frontier spectrophotometer (32 scans, 4000–650 cm⁻¹ wavenumber range) was used, and the spectra were evaluated based on wavenumber (cm⁻¹). Spectra were interpreted using Spectrum v2.0 Software. Subsequently, comparative analyses of the theoretically calculated IR spectra and the experimental spectra were performed. NMR analyses of the molecules were theoretically performed using ¹H-NMR and ¹³C-NMR spectra, which were re-optimized at the B3LYP/6-311++G(d,p) level in DMSO solvent using the IEFPCM method. ¹H and ¹³C-NMR chemical shift values were calculated using the standard GIAO/B3LYP/6-311++G(d,p) (Gauge-Independent Atomic Orbital) approach in DMSO solvent. Frontier orbitals (HOMO-LUMO) and molecular electrostatic potential (MEP) surfaces of the studied molecules were obtained using *chk files generated from the optimized structures, and these distributions and surfaces, which could play a leading role in drug design, were investigated. Because drug design has high time and cost requirements, computational drug design approaches developed in recent years have gained significant importance in reducing both time and cost. In silico methods are used to design drugs using pharmaceutical and organic chemical calculations. As part of our thesis, we used molecular docking, a molecular modeling technique, to elucidate the mechanisms of action of compounds. Schrödinger Maestro software was used to assess how compounds dock with amino acids in the enzyme's active site and to evaluate the interactions of compounds with high inhibitory activity.