Computational and pharmacological investigation of novel 1,5-diaryl-1,4-pentadien-3-one derivatives for analgesic, anti-inflammatory and anticancer potential
- سال انتشار: 1397
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 22، شماره: 1
- کد COI اختصاصی: JR_IJBMS-22-1_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 352
نویسندگان
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
LaBioMMi, Department of Chemistry, Federal University of São Carlos, CP ۶۷۶, ۱۳.۵۶۵-۹۰۵, São Carlos, SP, Brazil
چکیده
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.کلیدواژه ها
Analgesic, Anticancer, Anti-inflammatory, In silico studies, Miceاطلاعات بیشتر در مورد COI
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