Elucidating the structural basis for the enhanced antifungal activity of amide derivative against : a comprehensive computational investigation.

The continuous search for more effective options against well-known pathogens such as remains the rationale for the search for novel lead compounds from various sources. This study aims to investigate the chemical structure, chemical properties, of 5-(2-((5-(((1S,3R) -3-(5-acetamido-1,3,4-thiadiazolidin-2-yl) cyclopentyl) methyl)-1,3,4-thiadiazolidin-2-yl)amino)-2-oxoethyl)-2-methyl-2,3-dihydro-1H-pyrazol-3-ide designated ATCTP using DFT method ωB97XD/-311 +  + g(2d, 2p) and the biological potential of compound ATCTP against using molecular docking and ADMET studies. Geometry optimization was carried out in DMSO, ethanol. gas and water revealing minute discrepancies in bond length and wider differences in bond angles. Frontier molecular orbital investigations reveal HOMO-LUMO energy gap magnitude in decreasing order of ATCTP_Gas > ATCTP_Water > ATCTP_ethanol > ATCTP_DMSO inferring that water influences chemical stability of the compound the most compared to ethanol and DMSO. Density of state investigations have revealed electron density contributions at corresponding energy peaks. In silico pharmacokinetic predicts ATCTP not to be cytotoxic, hepatotoxic, immunotoxic or mutagenic but probable mutagen. Molecular docking investigation of ATCTP against aspartic proteinase of (ID: 2QZX) in comparison with standard drug Fluconazole. Compound ATCTP had higher binding affinity (- 8.1 kcal/mol) compared to that of the standard drug fluconazole (- 5.6 kcal/mol) which records 4 conventional hydrogen interactions compared to 2 formed in the interaction of ATCTP + 2QZX. ATCTP also reports binding affinity of - 7.2 kcal/mol which reportedly surpassed that of 2QZX interaction with fluconazole (- 5.7 kcal/mol). ATCTP binds with lanosterol14-α-demethylase (5v5z) with binding affinity of - 9.7 kcal/mol binding to active site amino acid residues of the protein compared to fluconazole + 5v5z (- 8.0 kcal/mol). ATCTP is therefore recommended to be a lead compound for the possible design of a new and more effective anti-candida therapeutic compound.