A novel synthesis, X-ray analysis and computational studies of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)- 4-oxo-3-phenylthiazolidin-2-ylidene)acetate as a potential anticancer agent

Yahia N Mabkhot; Mohammed M Alharbi; Salim S Al-Showiman; Saied M Soliman; Nabila A Kheder; Wolfgang Frey; Abdulrhman Asayari; Abdullatif Bin Muhsinah; H Algarni

doi:10.1186/s13065-019-0554-2

A novel synthesis, X-ray analysis and computational studies of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)- 4-oxo-3-phenylthiazolidin-2-ylidene)acetate as a potential anticancer agent

BMC Chem. 2019 Mar 26;13(1):35. doi: 10.1186/s13065-019-0554-2. eCollection 2019 Dec.

Authors

Affiliations

¹ 1Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha, 61441 Saudi Arabia.
² 2Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh, 11451 Saudi Arabia.
³ 3Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Alexandria, Ibrahimia-21321 Egypt.
⁴ 4Department of Chemistry, Rabigh College of Science and Art, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ 5Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613 Egypt.
⁶ 6Institut für OrganischeChemie, Universitӓt Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
⁷ 7Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha, 61441 Saudi Arabia.
⁸ 8Department of Physics, Faculty of Sciences, King Khalid University, P. O. Box 9004, Abha, Saudi Arabia.
⁹ 9Research Centre for Advanced Materials Science (RCAMS), King Khalid University, P. O. Box 9004, Abha, 61413 Saudi Arabia.

Abstract

Background: 4-Thiazolidinone ring is reported to have almost all types of biological activities. Also, it present in many marketed drugs.

Results: Ethyl acetoacetate reacted with phenyl isothiocyanate and ethyl chloroacetate in presence of K₂CO₃ and DMF to afford the thiazolidinone derivative 5. Thiazolidinone 5 reacted with dimethylformamide-dimethylacetal to afford (Z)-ethyl 2-((Z)-5-((dimethylamino) methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate (6). The structure of thiazolidinone 6 was elucidated from its spectral analysis and X-ray crystallography and was optimized using B3LYP/6-31G(d,p) method. The geometric parameters and NMR spectra were discussed both experimentally and theoretically. Also, the natural charges at the different atomic sites were predicted. The synthesized compounds had moderate cytotoxic activity.

Conclusions: An unexpected synthesis of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate via deacetylation mechanism. The structure was established using X-ray and spectral analysis. The geometric parameters, and NMR spectra were discussed. The synthesized compounds showed moderate anticancer activity.

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