title: Synthesis, Characterization and Molecular Docking of Novel Bioactive Thiazolyl-Thiazole Derivatives as Promising Cytotoxic Antitumor Drug.
abstract: Reactions of ethylidenethiocarbohydrazide with hydrazonoyl halides gave 1,3-thiazole or 1,3,4-thiadiazole derivatives according to the type of hydrazonoyl halides. Treatment of ethylidenethiosemicarbazide with hydrazonoyl halides and dimethylacetylene dicarboxylate (DMAD) afforded the corresponding arylazothiazoles and 1,3-thiazolidin-4-one derivatives, respectively. The structures of the synthesized products were confirmed by IR, ¹H-NMR, (13)C-NMR and mass spectral techniques. The cytotoxic activity of the selected products against the Hepatic carcinoma cell line (Hepg-2) was determined by MTT assay indicating a concentration dependent cellular growth inhibitory effect, especially for compounds 14c and 14e. The dose response curves indicated the IC50 (the concentration of test compounds required to kill 50% of cell population) were 0.54 μM and 0.50 μM, respectively. Confocal laser scanning imaging of the treated cells stained by Rhodamin 123 and Acridine orange dyes confirmed that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The binding mode of the active compounds was interpreted by a molecular docking study. The obtained results revealed promising cytotoxic activity.
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. s.m.gomha@hotmail.com.
authors.forename: Sobhi M
authors.initials: SM
authors.lastname: Gomha
authors.affiliation: Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza 12613, Egypt. t1salah@hotmail.com.
authors.forename: Taher A
authors.initials: TA
authors.lastname: Salaheldin
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt. huwaida30@gmail.com.
authors.forename: Huwaida M E
authors.initials: HM
authors.lastname: Hassaneen
authors.affiliation: Chemistry Department, Faculty of Science, Cairo University, Bani Suef Branch, Bani Suef 62514, Egypt. dr_hassan1971@yahoo.com.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt. mohammed_abdou0@yahoo.com.|Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, P. O. 380, Al-Hasaa 31982, Saudi Arabia. mohammed_abdou0@yahoo.com.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khedr
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase
keywords: 1,3,4-thiadiazole; 1,3-thiazole; cytotoxic activity; ethylidenethiocarbohydrazide; ethylidenethiosemicarbazide; hydrazonoyl halides; molecular docking