| Autor: |
Dadou S; Laboratory of Applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda, Morocco.; Laboratory of Molecular Chemistry, Materials and Environment, Polydisciplinary Faculty of Nador, Mohammed First University, Oujda, Morocco., Altay A; Department of Chemistry, Faculty of Arts and Science, Erzincan Binali Yıldırım University, Erzincan, Turkey., Baydere C; Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, Samsun, Turkey., Anouar EH; Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia., Türkmenoğlu B; Department of Analytical Chemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, Erzincan, Turkey., Koudad M; Laboratory of Molecular Chemistry, Materials and Environment, Polydisciplinary Faculty of Nador, Mohammed First University, Oujda, Morocco., Dege N; Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, Samsun, Turkey., Oussaid A; Laboratory of Molecular Chemistry, Materials and Environment, Polydisciplinary Faculty of Nador, Mohammed First University, Oujda, Morocco., Benchat N; Laboratory of Applied Chemistry and Environment, Faculty of Sciences, Mohammed First University, Oujda, Morocco., Karrouchi K; Laboratory of Analytical Chemistry and Bromatology, Team of Formulation and Quality Control of Health Products, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco. |
| Abstrakt: |
In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1 H NMR, 13 C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC 50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC 50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔG Bind ), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard.Communicated by Ramaswamy H. Sarma. |
