Background: Currently, clinically used drugs for internal fungal infections have severe
side effects. Patients suffering from severe fungal infections and those at a constant risk of developing
such infections require long-term administration of safe antifungals.
Objective: This work deals with the design and development of safe, non-toxic antifungals derived
from natural compounds for immune-compromised patients, such as HIV patients, who are at a constant
risk of developing internal fungal infections.
Methods: Molecular modeling, docking and molecular dynamics simulation studies were performed
on the main constituents of ginger and their derivatives to study their capability to inhibit 14α-
Results: Ergosterol is the key component of the fungal cell membrane for its integrity and rigidity,
synthesized from lanosterol catalyzed by 14α-demethylase enzyme. In our studies, it is determined
that 6-gingerol, 6-paradol, 6-shogaol and their imidazole and triazole derivatives can inhibit the synthesis
of ergosterol thus weakening the fungal cell membranes. The triazole derivative of 6-gingerol
forms enhanced binding interactions with the active site residues of 14α-demethylase, carries an
affinity for catalytically required cofactor heme and forms a stable complex with time without the
probability of premature expulsion. Thus, this compound inhibits the formation of ergosterol leading
to weakened fungal cell membranes and eventually death of fungal cells.
Conclusion: The triazole derivative of 6-gingerol is recommended as a lead compound for the development
of non-toxic antifungals.