Background: The multicomponent primary active ATP-binding cassette transporter Cdr1p in
the structure of the pathogenic yeast Candida albicans is among the culprits of antifungal agent resistance
reported in recent decades. So far, various potential novel inhibitors/ modulators of this protein
have been purified, synthesized, and biologically tested, with results showing their ability to effectively
reverse CaCdr1p-mediated drug resistance phenomenon. These compounds are of diverse origins, possess
non-identical structural features and adopt different mechanisms of action.
Method: A structured search of chemical features and mechanisms of studied modulators of CaCdr1p
was carried out using both original research publications and review articles. The nature of possible
inhibitory mechanisms against the pump was analyzed in relation to the structure and the activity of the
transporter. A process of summarizing modulatory spectra of the listed compounds against 2 other efflux
pumps of Candida albicans namely Cdr2p and Mdr1p was also conducted, during which selective
inhibitors of Cdr1p were revealed.
Results: In this article, 6 possible mechanisms with which a molecule can manifest their activity against
the efflux pump are described, and a list of nearly 50 CaCdr1p modulators found in literatures along
with their respective mechanism(s) (if already identified) is provided, summarizing the results obtained
so far in the search of new inhibitors of the drug extrusion transporter that can enhance the potency of
commonly used antifungal agents. A table of inhibitory spectra of the listed compounds against Cdr1p,
Cdr2p and Mdr1p is also given, with several selective modulators of Cdr1p finally indicated.
Conclusion: The findings of this review contribute to future studies regarding CaCdr1p and its modulators
by summarizing the results obtained so far on this emerging issue of health sciences. Further research
concerning novel compounds capable of inhibiting Cdr1p needs to be carried out in hopes of
completing the lists provided in this article.