Grinding-assisted synthesis of novel arylhydrazono curcumin analogues and bis-pyrazolines as cyclin-dependent kinases (CDKs) inhibitors

• Published in: Inorganic chemistry communications 2024-11, Vol.169, p.113128, Article 113128
• Main Authors: Gomha, Sobhi M., Riyadh, Sayed M., El-Sayed, Abdel-Aziz A.A., Abdallah, Abanoub M., Zaki, Magdi E.A., Alrehaily, Abdulwahed, Elbadawy, Hossein M., Al-Shahri, Ahmad A., Alsenani, Saleh R., Hussein, Ahmed M.
• Format: Article
• Language: English
• Subjects: Anticancer activity; Bis-chalcones; Bis-pyrazolines; Manual grinding; Molecular docking
• ISSN: 1387-7003
• DOI: 10.1016/j.inoche.2024.113128

[Display omitted] •Green technique: Manual grinding synthesis.•Novel compounds: Curcumin analogues, pyrazolines.•Objectives: Energy saving, high yield, atom economy.•Structural elucidation: Spectroscopic techniques employed.•Molecular docking: CDK2 binding site.•Promising compounds: 5c, 5i, 5f. The grinding method, an environmentally friendly technique in green chemistry, was employed for the efficient synthesis of heterocyclic compounds, specifically symmetrical curcumin analogues and bis-pyrazoline derivatives. This approach aimed to save energy, increase product yield, and achieve high atom economy compared to conventional methods. The synthesized compounds were characterized using spectroscopic techniques. Molecular docking simulations predicted the binding modes of these compounds within the CDK2 binding site, with compounds 5c, 5i, and 5f showing the highest binding energy scores (−14.77, −14.26, and −14.11 kcal/mol), indicating potential anticancer activity superior to the co-crystallized ligand. In vitro studies against HCT-116 cells confirmed that compound 5c exhibited the highest potency (IC50 = 3.48 ± 1.05 µM), suggesting its potential as a promising anticancer agent.