Reactivity Study, NCI-RDG Analysis, Molecular Docking and ADMET Investigation of N-(4-Acetyl-5-(4-(nitro)phenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-N-phenyl Acetamide

Abstract— The search for novel compounds with antimitotic properties has gained significant attention due to their potential to inhibit mitosis; which is crucial in cancer therapy as they can decrease the rapid division of cancer cells, potentially preventing tumor formation. In this study, we employed computational techniques, including DFT calculation, molecular docking and ADMET predictions to evaluate various properties such as chemical reactivity, intramolecular interactions, the inhibitory activity against an antimitotic target and pharmacokinetic properties of N-(4-acetyl-5-(4-(nitro)phenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)-N-phenyl acetamide (NTPA). DFT calculations show that this compound exhibits more reactivity in polar medium with an electrophilic character. NBO analysis shows that a charge transfer is carried out within different fragments of the title compound. Our findings shed light on the potential of the title compound as a promising candidate for further development as an anticancer agent. ADMET predictions show that NTPA compound exhibits appreciable physicochemical and pharmacokinetic properties.