Background: Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that
have been shown to be involved in the development of multi-drug resistance (MDR) mechanism toward chemotherapeutic
agents. GST inhibitors have, therefore, emerged as promising chemosensitizers to manage and
reverse MDR. Colchicine (COL) is a classical antimitotic, tubulin-binding agent (TBA) which is being explored
as anticancer drug.
Methods: In the present work, the interaction of COL and its derivative 2,3-didemethylcolchicine (2,3-DDCOL)
with human glutathione transferases (hGSTA1-1, hGSTP1-1, hGSTM1-1) was investigated by inhibition analysis,
molecular modelling and molecular dynamics simulations.
Results: The results showed that both compounds bind reversibly to human GSTs and behave as potent inhibitors.
hGSTA1-1 was the most sensitive enzyme to inhibition by COL with IC50 22 μΜ. Molecular modelling predicted
that COL overlaps with both the hydrophobic (H-site) and glutathione binding site (G-site) and polar interactions
appear to be the driving force for its positioning and recognition at the binding site. The interaction of COL with
other members of GST family (hGSTA2-2, hGSTM3-3, hGSTM3-2) was also investigated with similar results.
Conclusion: The results of the present study might be useful in future drug design and development efforts towards