Synthesis, Molecular Modeling, and Anticancer Screening of Some New Imidazothiadiazole Analogs

Abstract

A series of N-aryl-2-((6-arylimidazo[2,1-b]thiadiazol-2-yl)thio)acetamide compounds 4 and 5 was synthesized by heterocyclization of their precursors N-aryl-2-((5-amino-1,3,4-thiadiazol-2-yl)thio)acetamides 3a–c with phenacyl chloride reagents. The structural and spectral features of the synthesized compounds were studied using DFT calculations. The DFT-estimated ¹H NMR spectral data exhibited good agreement with the experimental data. Furthermore, the HOMO–LUMO energies were used in determination of some chemical reactivity descriptors. The cytotoxic activities of the prepared imidazothiadiazoles were evaluated toward four different cancer cell lines. Derivatives 5c, 4c, 5a, and 4a presented powerful cytotoxic results against breast cancer rather than the residual derivatives 5b and 4b compared with 5-fluorouracil as a reference. Meantime, the docking study was used on the synthesized imidazothiadiazole analogs and furnished adequate results toward PDB ID: 1DLS.

Keywords:

• Breast cancer
• 2-chloroacetamides
• Fukui’s indices
• imidazothiadiazoles
• molecular docking
• Mulliken’s charges

Disclosure statement

The author declares that there is no conflict of interest regarding the publication of this paper.