Screening the cholinesterase inhibitory potential of some (1E, 4E)-1.5- diphenylpenta-1.4-dien-3-one derivatives

Yıl 2019, Cilt: 2 Sayı: 1, 7 - 12, 11.09.2019

Açelya Mavideniz Amirhossein Fallah Foroogh Koshravi Farimah Ahdno Mehmet Arter Tuğba Erçetin Mustafa Fethi Sahin Hayrettin Ozan Gülcan

Öz

α,β-unsaturated ketones are particularly important scaffolds to be
utilized in diverse organic reactions including the synthesis of many heterocyclics.
Regarding their reactivities as electrophiles, their nature to be utilized as
drug candidates are quite limited, although there are natural molecules with
diverse pharmacological activities whivh are known to have α,β-unsaturated
functionalization. Within this preliminary and random drug-screening based
medicinal chemistry study, some (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one
derivatives were synthesized and their structures were identified employing
chromatographic and spectral methods. The potential of the compounds to inhibit
acetylcholinesterase and butyrylcholinesterase enzymes was measured employing
modified Ellman’s method. Although the compounds were not found to be potent
inhibitors in comparison to current drugs, their activity spectra and
selectivity properties displayed their availability to be utilized as important
scaffolds for further design of similar α,β-unsaturated systems.

Anahtar Kelimeler

acetylcholinesterase, butyrylcholinesterase, α, β-, unsaturated ketones

Kaynakça

• Deardorff WJ, Feen E, Grossberg GT (2015). The use of cholinesterase inhibitors across all stages of Alzheimer’s disease. Drugs Aging 32(7): 537-547.
• Ferreira-Vieira H, Guimaraes TM, Silva IR, Ribeiro F (2016). Alzheimer's disease: targeting the cholinergic system. Cur Neuropharmaco 14(1): 101-115.
• Gulcan HO, Unlu S, Esiringu I, Ercetin T, Sahin Y, Oz D, Sahin MF (2014). Design, synthesis and biological evaluation of novel 6H-benzo [c] chromen-6-one, and 7, 8, 9, 10-tetrahydro-benzo [c] chromen-6-one derivatives as potential cholinesterase inhibitors. Bioorg Med Chem 22(19): 5141-5154.
• Kumar A, Singh A (2015). A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep 67(2): 195-203.
• Selkoe DJ (2001). Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81(2): 741-766.
• Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MR (1982). Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215(4537): 1237-1239.