Efficient synthesis of N-(ethylcarbamothioyl)-1-naphthamide: X-ray structure, Hirshfeld surface analysis, DFTs, and molecular modelling investigations as selective inhibitor of alkaline phosphatase.

Abstract

Naphthyl Thiourea based derivative N-(ethylcaramothbioyl)-1-naphthamide (NA-MT) was synthesized by freshly prepared 1-naphthoyl isothiocyanate with ethyl amine to afford the products (NA-MT) high purity and characterized via spectroscopic techniques including FTIR, ¹H-NMR, ¹³C-NMR, elemental and HRMS analysis and single crystal X-ray diffraction. In-vitro analysis showed that the compound (NA-MT) possesses potent inhibitory effect with IC₅₀ = 9.875 ± 0.05 surpassing its reference inhibitor L-phenyl alanine (IC₅₀ = 80.2 ± 1.1) against cIAP. Additionally, the synthesized derivative (NA-MT) underwent an in-depth analysis of its electronic properties and reactivity using Density Functional Theory (DFT) calculations. Evaluations using SwissADME revealed the compound (NA-MT) possess acceptable physicochemical attributes, such as solubility and drug-likeness. Molecular docking studies demonstrated the compound (NA-MT) exhibit strong binding affinities to cIAP, which were further validated via Molecular Dynamics (MD) simulations. These integrated experimental and computational tools highlight the potential therapeutic uses of the synthesized compound, and pave the way for the development of novel pharmacologically active Alkaline phosphatase inhibitors with diverse applications.