Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential

Document Type: Original Article


1 Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan

2 LaBioMMi, Department of Chemistry, Federal University of São Carlos, CP 676, 13.565-905, São Carlos, SP, Brazil

3 Department of Chemistry, Woman University Swabi, Guloo Dehri, Topi Road, 23340 Swabi, KPK, Pakistan

4 Basic Sciences Department, College of Science and Health Professions-(COSHP-J) King Saud bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia


Objective(s): The novel 1,5-diaryl-1,4-pentadien-3-one derivatives were studied for analgesic, anti-inflammatory and anticancer potential to establish their role in pain, inflammatory disorders and cancer.
Materials and Methods: Two 1,5- diaryl-1,4-pentadien-3-one derivatives: (1E,4E)- 5-(4-fluoro phenyl)-1-(4-methoxyphenyl)- 2-methylpenta-1,4-dien-3-one (A2K2A17) and  (1E,4E)-5-(4-nitrophenyl)-1-(4-nitrophenyl)-2-ethylhexa-1,4-dien-3-one (A11K3A11) were synthesized and characterized via 1H NMR and 13C NMR techniques. Molecular docking, anti-inflammatory, analgesic and anticancer activities were performed using Auto Doc Vina, carrageenan mediated paw edema and formalin induced chronic inflammation, acetic acid induced writhings and hotplate assay and brine-shrimp lethality assay.
Results: A2K2A17 and A11K3A11 showed high computational affinities (binding energy > -9.0 Kcal/mol) against COX-1, kappa receptor and braf kinase domain. A2K2A17 and A11K3A11 exhibited moderate docking affinities (binding energy > -8.0 Kcal/mol) against COX-2, human capsaicin receptor, tumor necrosis factor, lipoxygenase, colony stimulating factor, delta receptor, cyclin dependent protein kinase-2, mitogen activated kinase, mu receptor and kit kinase domain. A2K2A17 and A11K3A11 possess low docking affinities (binding energy > -7.0 Kcal/mol) against purinoceptor, platelets-derived growth Factor-1 and vascular-endothelial growth factor. In analgesic activity, A2K2A17 (1-30 mg/kg) and A11K3A11 (1-10 mg/kg) decreased acetic acid induced writhes and prolonged the latency time (P<0.01, PConclusion: The in silico, in vitro and in vivo studies on A2K2A17 and A11K3A11 reports their computational binding affinities against targets as well as the analgesic, anti-inflammatory and the anticancer effects.


Main Subjects

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