Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents

• Published in: BMC chemistry 2018-05, Vol.12 (1), p.56-9, Article 56
• Main Authors: Mabkhot, Yahia N., Alharbi, Mohammed M., Al-Showiman, Salim S., Ghabbour, Hazem A., Kheder, Nabila A., Soliman, Saied M., Frey, Wolfgang
• Format: Article
• Language: English
• Subjects: Anticancer properties; Atomic structure; Biological computing; Cancer; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Computational studies; Cytotoxic activity; Derivatives; Dimethyl acetals; DMF-DMA; Electropositivity; Energy gap; Molecular chains; Molecular orbitals; Organic and Medicinal Chemistry; Research Article; Synthesis; Thiazoles; X ray analysis; X-ray crystallography
• ISSN: 1752-153X; 1752-153X; 2661-801X
• DOI: 10.1186/s13065-018-0420-7

Background The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. Results Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6 , which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11 . The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. Conclusions Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6 . The HOMO–LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.