Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study
Ali, I., El Kerdawy, A., Batran, R., Allam, R., Abo-elfadl, M., Sciandra, F., Ghannam, I. (2024). Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study. EKB Journal Management System, 67(12), 111-127. doi: 10.21608/ejchem.2024.288226.9691
Islam Ali; Ahmed M El Kerdawy; Rasha Zakaria Batran; Rasha Mosa Allam; Mahmoud Taha Abo-elfadl; Francesca Sciandra; Iman Ahmed Youssef Ghannam. "Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study". EKB Journal Management System, 67, 12, 2024, 111-127. doi: 10.21608/ejchem.2024.288226.9691
Ali, I., El Kerdawy, A., Batran, R., Allam, R., Abo-elfadl, M., Sciandra, F., Ghannam, I. (2024). 'Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study', EKB Journal Management System, 67(12), pp. 111-127. doi: 10.21608/ejchem.2024.288226.9691
Ali, I., El Kerdawy, A., Batran, R., Allam, R., Abo-elfadl, M., Sciandra, F., Ghannam, I. Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study. EKB Journal Management System, 2024; 67(12): 111-127. doi: 10.21608/ejchem.2024.288226.9691

Discovery of Novel N-Acetylpyrazolines as Microtubule Inhibitors: Design, Synthesis, Anticancer Evaluation, and Molecular Docking Study

Egyptian Journal of Chemistry
Volume 67, Issue 12, December 2024, Page 111-127  XML PDF (1.64 MB)
Document Type: Original Article
DOI: 10.21608/ejchem.2024.288226.9691
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Authors
Islam Ali1; Ahmed M El Kerdawyorcid 2; Rasha Zakaria Batran1; Rasha Mosa Allamorcid 3; Mahmoud Taha Abo-elfadlorcid 4; Francesca Sciandra5; Iman Ahmed Youssef Ghannam email orcid 1
1National Research Centre (NRC)
2Pharmaceutical chemistry department, Faculty of Pharmacy Cairo University
3Department of pharmacology - National Research Centre
4Cancer Biology and Genetics Laboratory Centre of Excellence for Advanced Sciences, National Research Centre
5CNR - Italy
Abstract
In the current study, a new series of N-acetylpyrazolines (6a-d) were designed and synthesized from their corresponding chalcones and hydrazine hydrate in acidic medium. The N-acetylpyrazolines (6a-d) were tested for their anti-hepatocellular activity against liver cancer (Huh-7, and HepG-2), and normal BNL cell lines and compared with paclitaxel, colchicine, and combrestatin A-4 (CA-4), as standards, and their IC50 values were determined. The 3’,4’,5’-trimethoxyphenyl N-acetylpyrazoline derivative 6d was the found the most potent N-acetylpyrazoline derivative IC50 = 0.30, and 77.30 µM, respectively, and found non-cytotoxic to the normal BNL cell line. While compounds 6b, and 6c revealed lower anticancer activity against Huh-7 cell line IC50 = 14.50, and 11.00 µM, respectively. Moreover, the N-acetylpyrazolines 6a-d were evaluated for their anticancer screening against different cancer cell lines at 10 µM by the Developmental Therapeutic Program (DTP) - NCI - USA, and they showed mean GI% ranges 8.87-64.54%. The 3’,4’,5’-trimethoxyphenyl N-acetylpyrazolines 6c, and 6d revealed potent anticancer activities and lethal effects against lung cancer cell line (HOP-92) for 6c and melanoma cell line (SK-MEL-5) for 6d with GI% values of 104.80, and 109.52%, respectively. Furthermore, the N-acetylpyrazolines 6a-d enhanced tublin polymerization, and showed tubulin-stabilizing effects as paclitaxel at 50 µM. A molecular docking study was performed for the N-acetylpyrazolines 6a-d to investigate the binding pattern at the Taxol-binding site of microtubules.
Keywords
N-acetylpyrazolines; Tubulin polymerization inhibitors; Anticancer activity; Molecular docking study
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