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

Yahia N Mabkhot; Mohammed M Alharbi; Salim S Al-Showiman; Hazem A Ghabbour; Nabila A Kheder; Saied M Soliman; Wolfgang Frey

doi:10.1186/s13065-018-0420-7

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

Chem Cent J. 2018 May 11;12(1):56. doi: 10.1186/s13065-018-0420-7.

Authors

Yahia N Mabkhot¹, Mohammed M Alharbi², Salim S Al-Showiman², Hazem A Ghabbour^{3

4}, Nabila A Kheder^{5

6}, Saied M Soliman^{7

8}, Wolfgang Frey⁹

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh, 11451, Saudi Arabia. yahia@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh, 11451, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia.
⁴ Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, 35516, Egypt.
⁵ Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt.
⁶ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Khalid University, Abha, 61441, Saudi Arabia.
⁷ Department of Chemistry, Rabigh College of Science and Art, 344, Rabigh, 21911, Saudi Arabia.
⁸ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria, 21321, Egypt.
⁹ Institut für Organische Chemie, Universitӓt Stuttgart, Pfaffenwaldring 55, 70569, Stuttgart, Germany.

Abstract

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.

Keywords: Computational studies; Cytotoxic activity; DMF-DMA; Thiazoles; X-ray crystallography.