1. Bioactive constituents from Thunbergia erecta as potential anticholinesterase and anti-ageing agents: Experimental and in silico studies.
- Author
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Refaey, Mohamed S., Abdelhamid, Reda A., Elimam, Hanan, Elshaier, Yaseen A.M.M., Ali, A.A., and Orabi, Mohamed A.A.
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TELOMERASE reverse transcriptase , *CHOLINESTERASE inhibitors , *ACETYLCHOLINESTERASE , *AMINO acid residues , *ESSENTIAL amino acids , *REVERSE transcriptase inhibitors - Abstract
• Ten known compounds were isolated from Thunbergia erecta aerial parts. • Their activities as anticholinesterase and as telomerase reverse transcriptase potentiator were evaluated. • In silico studies including molecular docking and ROCS analysis as anticholinesterase were implemented. • In silico studies in addition to SPR displayed the most important pharmacophoric features. • Compound 2 is reliable for further studies utilizing semisynthetic strategy as a lead candidate. Acetylcholinesterase (AChE) inhibitor and telomerase reverse transcriptase (TERT) potentiator phytochemicals are highly targeted as anti-Alzheimerꞌs disease and as an anti-ageing process. A phytochemical study of Thunbergia erecta aerial parts resulted in the isolation of ten compounds (1 – 10). Their structures were identified based on spectral data and comparison with literature values. The activity of our pure isolates on AChE and TERT enzymes by documented in vitro assay methods were evaluated. The results indicated that apigenin (2), vanillic acid (4), and acacetin-7- O - β -D-glucoside (7) exhibited potent inhibition of AChE (IC 50 37.33, 30.80 and 49.57 ng/mL, respectively), compared to the standard drug donepezil (IC 50 31.25 ng/mL). In the TERT enzyme assay, compound 7 triggered a 1.66‑fold increase in telomerase activity at the concentration of 2.85 ng/ml. This is the first study that demonstrates that compound 7 isolated from T. erecta can lead to such telomerase activity relative to control cells. Virtual screening studies including docking, rapid overlay chemical structure (ROCS), and calculated structure–property relationships (SPR) were implemented in this work. Molecular docking studies supported the binding of compounds 2 , 4 , and 7 through hydrogen bonds (HBs) formation to essential amino acid residues namely ARG:24 A, SER:347 A, LYS:51 A, PHE:346 A, and GLY:345 A of acetylcholinesterase. ROCS and SPR analyses realized compound 2 as a possible treatment of Alzheimer's disease and as a lead compound for drug development process through applying semisynthetic modifications. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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