Theoretical study of the geometric and electronic characterization of carbendazim-based drug (Nocodazole)

Abstract

Scarcity in studies defining the precise three-dimensional structure of approved drugs has led to an abandoning of their use for other therapeutic indications. In this manuscript, we solely focus on studying computationally the anticancer drug "Nocodazole" as a model compound for anthelmintic drugs -due to structural similarity-proven to exert anticancer activity such as Mebendazole and Albendazole. Computations on Nocodazole structures deposited in the Protein Data Bank (PDB) revealed possible existence of at least 6 conformers of Nocodazole. By combining the reported experimental UV-Vis data with our calculations, two conformers were assigned as the predominant structures of Nocodazole. In addition, td-DFT calculations revealed that the conformational flexibility of Nocodazole results in significant changes in atomic and molecular charge densities. The results have ramifications in identification of possible conformers of carbendazim-based drugs for repurposing in oncology through giving deep insights in understanding the spatial and electronic changes upon drug binding to anticancer targets.

Revisiting Activity of Some Nocodazole Analogues as a Potential Anticancer Drugs Using Molecular Docking and DFT Calculations

“…The first seven members of the nine elected benzimidazole anthelmintic drugs (1-7) exhibit structural similarity (benzimidazole core and carbamate moiety) with NZO. Studies reported here is a continuation to our previous work on NZO and a benzimidazole-based anthelmintic drug (Mebendazole) (Al-Karmalawy and Khattab, 2020;Khattab, 2020).…”

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

“…It is well known that the outermost orbitals contribute most to the drug–receptor interactions; therefore, the charge density values of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were calculated. The energy gap between HOMO and LUMO indicates the energy contribution to the covalent bond formation [ 35 , 36 ]. The graphical representations of the outermost orbitals’ electronic densities are listed in Table 4 .…”

Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study

“…The ECD spectrum measures the difference in absorbance of right- and left-circularly polarized light by a molecule rather than the commonly used absorbance of isotropic light as in UV-vis measurements. 44 The ECD spectra of ciclesonide 11 calculated at the B3LYP/6-311G* and B3LYP/6-311+G* levels are reported for the first time, as depicted in Table 6 .…”