Ligand-guided investigation of a series of formamidine-based thiuram disulfides as potential dual-inhibitors of COX-1and COX-2

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Authors

Oladipo, Segun D.
Akinpelu, Olayinka I.
Omondi, Bernard

Journal Title

Journal ISSN

Volume Title

Publisher

Wiley

Abstract

A series of thiuram disulfides 1–6 which had been previously synthesized and characterized, were studied for their potential therapeutic properties. Target-fishing analyses through HitPick and SwissTarget prediction identified COX1 and COX2, which are essential biomolecules in cancer-related inflammations, as the possible targets for compounds 1 and 4 among all the compounds tested. These two proteins have enjoyed interest as targets for treating some neoplastic cancer types such as breast, colorectal, skin, pancreatic, haematological and head cancers. The inhibitory potency of 1 and 4 as lead anticancer drug candidates with dual-target ability against COX1 and COX2 was examined through molecular docking, molecular dynamics simulation and post-MD analyses such as binding energy calculation, RMSD, RMSF, and RoG. The two compounds had better docking scores and binding energies than the known inhibitors of COX1 and COX2. Insights from the RMSD, RMSF, and RoG suggested that both 1 and 4 showed observable influence on the structural stability of these targets throughout the simulation. The reported observations of the effects of 1 and 4 on the structures of COX1 and COX2 indicate their probable inhibitory properties against these target proteins and their potential as lead anticancer drug candidates.

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DATA AVAILABILITY STATEMENT : The data that support the findings of this study are available in the supplementary material of this article.

Keywords

Thiuram disulfide, Cyclooxygenase 1 and 2, Molecular docking, Binding energy, SDG-03: Good health and well-being

Sustainable Development Goals

SDG-03:Good heatlh and well-being

Citation

Oladipo, S.D., Akinpelu, O.I., Omondi, B. 2023, 'Ligand-guided investigation of a series of formamidine-based thiuram disulfides as potential dual-inhibitors of COX-1and COX-2', Chemistry and Biodiversity, vol. 20, art. e202200875, p. 1-15. DOI.org/10.1002/cbdv.202200875.