Camptothecin shows better promise than Curcumin in the inhibition of the Human Telomerase: A computational study

Abstract

Objectives The Human Telomerase enzyme has become a drug target in the treatment of cancers and age-related disorders. This study aims to identify potential natural inhibitors of the Human Telomerase from compounds derived from edible African plants. Materials and methods A library of 1,126 natural compounds was molecularly docked against the Telomerase Reverse Transcriptase (PDB ID: 5ugw), the catalytic subunit of the target protein. Curcumin, a known Telomerase inhibitor was used as the standard. The front-runner compounds were screened for bioavailability, pharmacokinetic properties, and bioactivity using the SWISSADME, PKCSM, and Molinspiration webservers respectively. The molecular dynamic simulation and analyses of the apo and holo proteins were performed by the Galaxy supercomputing webserver. Results The results of the molecular docking and virtual screening reveal Augustamine and Camptothecin as lead compounds. Augustamine has better drug-likeness and pharmacokinetic properties while Camptothecin showed better bioactivity and stronger binding affinity (-8.2 kcal/mol) with the target. The holo structure formed by Camptothecin showed greater inhibitory activity against the target with a total RMSF of 169.853, B-Factor of 20.164, and 108 anti-correlating residues. Conclusion Though they both act at the same binding site, Camptothecin induces greater Telomerase inhibition and better molecular stability than the standard, Curcumin. Further tests are required to investigate the inhibitory activities of the lead compounds.

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

“…Theranekron D6 (Tosun et al, 2021) obtained from spider venom and gaillardin (Roozbehani et al, 2021) isolated from Inula oculus-christi have attracted great attention due to their significant proapoptotic properties, and therefore, they may be powerful candidates for inducing apoptosis in the future. Camptothecin, curcumin (Rowaiye et al, 2021), isoquinoline alkaloids of Chelidonium majus (Noureini et al, 2017), amentoflavone (Revikumar, 2021), and emodin (Liu et al, 2019), are effective telomerase inhibitors. Some natural compounds, such as fucoidan (Yang et al, 2021), myricetin (Ghassemi-Rad et al, 2018, bergapten (Xie et al, 2018), and atractylenolide I (Xu et al, 2021), have good immunomodulatory effects so that they have great potential as candidates for immunotherapy in the future.…”