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Novel pyrimidine Schiff bases and their selenium-containing nanoparticles as dual inhibitors of CDK1 and tubulin polymerase: design, synthesis, anti-proliferative evaluation, and molecular modelling
Faculty
Science
Year:
2023
Type of Publication:
ZU Hosted
Pages:
Authors:
Mustafa Salahuddin Abdul Hamid Hasan
Staff Zu Site
Abstract In Staff Site
Journal:
Journal of Enzyme Inhibition and Medicinal Chemistry Informa UK Limited, trading as Taylor & Francis Group
Volume:
Keywords :
Novel pyrimidine Schiff bases , their selenium-containing
Abstract:
Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases (4-9) were employed in the synthesis of selenium nanoparticle forms (4NPs-9NPs). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound 4 showed effective anti-proliferative activity against MCF-7(IC50 3.14 ± 0.04 µM), HepG-2(IC50 1.07 ± 0.03 µM), and A549(IC50 1.53 ± 0.01 µM) cell lines, while its selenium nanoform 4NPs showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, 4NPs outperformed 4 in selectivity against the Vero cell line by 4.5-fold. Furthermore, 4NPs exhibited strong inhibition of CDK1(IC50 0.47 ± 0.3 µM) and tubulin polymerase(IC50 0.61 ± 0.04 µM), outperforming 4 and being comparable to roscovitine (IC50 0.27 ± 0.03 µM) and combretastatin-A4(IC50 0.25 ± 0.01 µM), respectively. Moreover, both 4 and 4NPs arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that 4 and 4NPs were able to inhibit CDK1 and tubulin polymerase binding sites.
Author Related Publications
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Mustafa Salahuddin Abdul Hamid Hasan, "In Vivo Biological Evaluation of Ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1-ylamino)-coumarin-3-carboxylate as an Antitumor Agent", Bentham Science Publishers, 2020
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Mustafa Salahuddin Abdul Hamid Hasan, "Synthesis and molecular docking of hybrids ionic azole Schiff bases as novel CDK1 inhibitors and anti-breast cancer agents: In vitro and in vivo study", ScienceDirect, 2021
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Mustafa Salahuddin Abdul Hamid Hasan, "Study of the protective and antioxidant activities of the extract of nelumbo nucifera seed against CCL4-induced damage of liver and kidney in female rats", Folium Publishing Company, 2015
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