X-ray crystallographic study, molecular docking, molecular dynamics and DFT/ADMET analyses of carboxylsulfamides.

• The elucidation of the crystal structure of compound 4a has been achieved, revealing that the crystals exhibit orthorhombic symmetry, and are classified within the p 2 1 2 1 2 1 space group. • Molecular docking study was carried out to give insights into the interactions of six derivativeswith the binding sites ofglutamate carboxypeptidase II (GCP2). • The drug-likeness property of the substance was evaluated via pharmacokinetic analysis. • Electronic structure calculations based on density functional theory (DFT) have been conducted at the B3LYP/6–31 G (d, p) level of theory. Because of their superior anticancer activity, pharmacokinetic capabilities, their chemical and enzymatic stability many compounds containing N -acylsulfonamide have been used as enzymatic inhibitors. In the present study, a series of novel carboxylsulfamides containing N -acylsulfonamide moiety were synthesized and screened for anticancer activity. The structure of carboxylsulfamide has been determined by X-ray diffraction. It is crystallized in the orthorhombic crystal system with P 2 1 2 1 2 1 space group. The crystal packing for Boc-sulfonamidecan be described as alternating layers parallel to (011) plane. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties. Molecular docking was conducted against glutamate carboxypeptidase II (GCP2) and revealed binding affinities. Then, a 50 ns molecular dynamic simulation was performed to confirm the behavior of the complex structure formed by cancer protein under in silico physiological conditions to examine its stability over time, which revealed a stable conformation and binding pattern in a stimulating environment of carboxylsulfamide derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]