title: Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer's disease candidates: Evidences-based on in vivo study.
abstract: Alzheimer's disease (AD) is a complex disease in which a single monofunctional 'targeted' drug is uneffective for management. Hybrid drugs that impact multiple targets simultaneously are better at controlling such complex disease systems. Hybrid agents were synthesized through the combination of the steroid moiety with curcumin molecule. Also novel curcumin analogues containing promising heterocyclic nucleus fused to the essential pharmacophoric feature of the curcumin moiety, were synthesized. The aim of the present study was extended to elucidate the efficacy of these novel synthesized compounds in the regression of AD induced in adult female albino rats. The results revealed that treatment of AD groups with compounds 3, 5, 8c or rivastigmin experienced significant increase in brain Ach, GSH, paraoxenase and BCL2 levels with respect to untreated group associated with significant decrease in brain AchE activity, urinary 8-OHG level, serum Caspase-3 level and brain P53 level relative to the untreated group. Immunohistochemical investigation revealed that the selected treatments caused marked increase in ChAT positive cells. These findings were documented by the histological investigation of the brain tissue. The activity of tested compounds showed gradual increase from compound b followed by compound 8c then compound 5. The anti-cholinesterase potential, anti-oxidant properties and anti-apoptotic activity are responsible for the anti-Alzheimer's disease potential of these compounds.
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt(1). Electronic address: gamalae@hotmail.com.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Elmegeed
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt(1).
authors.forename: Hanaa H
authors.initials: HH
authors.lastname: Ahmed
authors.affiliation: Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
authors.forename: Maher A
authors.initials: MA
authors.lastname: Hashash
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt(1).
authors.forename: Mervat M
authors.initials: MM
authors.lastname: Abd-Elhalim
authors.affiliation: Hormones Department, National Research Centre, Dokki, Giza, Egypt(1).
authors.forename: Dina S
authors.initials: DS
authors.lastname: El-kady
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003474:Curcumin / Q000737:chemistry*; D005260:Female; D016877:Oxidants / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D013256:Steroids; D016159:Tumor Suppressor Protein p53; D002795:Choline O-Acetyltransferase; D053148:Caspase 3; D003474:Curcumin; D000109:Acetylcholine
keywords: Alzheimer’s disease; Curcumin analogues; Heterocycles; Rats