Affiliation:
1. Laboratory of Medicinal Chemistry Faculty of Medicine and Pharmacy Mohammed V University 10100 Rabat Morocco
2. Department of Chemistry Faculty of Arts and Science Erzincan Binali Yıldırım University 24002 Erzincan Turkey
3. Laboratory of Analytical Chemistry and Bromatology Faculty of Medicine and Pharmacy Mohammed V University 10100 Rabat Morocco
4. Department of Chemistry Institute of Science and Technology Erzincan Binali Yıldırım University 24002 Erzincan Turkey
5. Department of Analytical Chemistry Faculty of Pharmacy Erzincan Binali Yıldırım University 24002 Erzincan Turkey
Abstract
AbstractIn this work, the design, synthesis, and mechanistic studies of novel pyrazole‐based benzofuran derivatives 1–8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A‐549, human‐derived colorectal adenocarcinoma HT‐29, breast adenocarcinoma MCF‐7 cells as well as mouse fibroblast 3T3‐L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose‐dependent anti‐proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti‐proliferative activity with an IC50 value of 7.31 μM and the highest selectivity (15.74) on MCF‐7 cells. Flow cytometry results confirmed that the cytotoxic power of compound 2 on MCF‐7 cells is closely related to mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase‐3 via in‐silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.
Funder
Université Mohammed V de Rabat
Subject
Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering