Neuroprotective Potential of Synthetic Mono-Carbonyl Curcumin Analogs Assessed by Molecular Docking Studies

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-11, Vol.26 (23), p.7168
• Main Authors: Hussain, Haya, Ahmad, Shujaat, Shah, Syed Wadood Ali, Ghias, Mehreen, Ullah, Abid, Rahman, Shafiq Ur, Kamal, Zul, Khan, Farman Ali, Khan, Nasir Mehmood, Muhammad, Juma, Almehmadi, Mazen, Abdulaziz, Osama, Alghamdi, Saad
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amnesia; Amnesia - chemically induced; Amnesia - diagnostic imaging; Amnesia - drug therapy; Amnesia - pathology; Analogs; Animal models; Animals; Carbonyl compounds; Carbonyls; Catalytic Domain - drug effects; Cholinergic Agents - chemical synthesis; Cholinergic Agents - chemistry; Cholinergic Agents - pharmacology; Cholinergic transmission; Cholinergics; Cholinesterase; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; cholinesterases; Cholinesterases - drug effects; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - pathology; Curcumin; Curcumin - analogs & derivatives; Curcumin - chemical synthesis; Curcumin - chemistry; Curcumin - pharmacology; Dementia; Dementia - chemically induced; Dementia - diagnostic imaging; Dementia - drug therapy; Dementia - pathology; Dementia disorders; Drug dosages; Enzymes; EPM; Hippocampus - diagnostic imaging; Hippocampus - drug effects; Hippocampus - pathology; Humans; Hypotheses; In vivo methods and tests; Ligands; Maze Learning - drug effects; Memory; Memory - drug effects; Mice; Molecular docking; Molecular Docking Simulation; mono-carbonyl curcumin analogs; Neuroprotection; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Pattern recognition; Scopolamine; Scopolamine - toxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237168

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound ( 0.001) and ( 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT ( 0.001) in EPM, while ( 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased ( 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.