Pharmacophore mapping approach to find anti-cancer phytochemicals with metformin-like activities against transforming growth factor (TGF)-beta receptor I kinase: An in silico study.

Autor: Reza R; Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh., Morshed N; Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh., Samdani MN; Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh., Reza MS; Department of Pharmaceutical Technology, University of Dhaka, Dhaka, Bangladesh.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Nov 09; Vol. 18 (11), pp. e0288208. Date of Electronic Publication: 2023 Nov 09 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0288208
Abstrakt: The most frequently prescribed first-line treatment for type II diabetes mellitus is metformin. Recent reports asserted that this diabetes medication can also shield users from cancer. Metformin induces cell cycle arrest in cancer cells. However, the exact mechanism by which this occurs in the cancer system is yet to be elucidated. Here, we investigated the impact of metformin on cell cycle arrest in cancer cells utilizing transforming growth factor (TGF)-beta pathway. TGF-ß pathway has significant effect on cell progression and growth. In order to gain an insight on the underlying molecular mechanism of metformin's effect on TGF beta receptor 1 kinase, molecular docking was performed. Metformin was predicted to interact with transforming growth factor (TGF)-beta receptor I kinase based on molecular docking and molecular dynamics simulations. Furthermore, pharmacophore was generated for metformin-TGF-ßR1 complex to hunt for novel compounds having similar pharmacophore as metformin with enhanced anti-cancer potentials. Virtual screening with 29,000 natural compounds from NPASS database was conducted separately for the generated pharmacophores in Ligandscout® software. Pharmacophore mapping showed 60 lead compounds for metformin-TGF-ßR1 complex. Molecular docking, molecular dynamics simulation for 100 ns and ADMET analysis were performed on these compounds. Compounds with CID 72473, 10316977 and 45140078 showed promising binding affinities and formed stable complexes during dynamics simulation with aforementioned protein and thus have potentiality to be developed into anti-cancer medicaments.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Reza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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