Development of Drug Resistance in Trichomonas vaginalis and its Overcoming with Natural Products

Abstract

Trichomoniasis is an infectious disease afflicting women worldwide. The protozoan parasite Trichomonas vaginalis is the causative agent of this sexually-transmitted disease, including also men in its infection cycle. The disease is usually not life-threatening, but has been associated with the development of cervical cancer and increased susceptibility to HIV. Approved drugs are 5-nitroimidazoles, with metronidazole being the drug of first choice. These drugs act via induction of oxidative stress and DNA-damage, leading to cell death in the parasite. Nevertheless, with the development of resistant T. vaginalis strains the treatment of the disease becomes exceedingly difficult. Mechanisms of drug resistance are characterized by reduced expression or even loss of proteins necessary for drug activation and a decreased reductive nature in the parasite. A promising strategy for research into new drugs and moreover, to overcome drug resistance, are compounds derived from natural sources. The present study provides a summary of all so far investigated small molecules with antitrichomonal activity; promisingly, some also show efficacy against resistant strains. Whereas the list of chemically characterized compounds derived from plants is rather short, literature provides immense applications of crude plant extracts tested against T. vaginalis. This demonstrates the absence of studies in this field aimed to identify and isolate single natural products exhibiting antitrichomonal features. Likewise, elucidating their mode of action on a molecular basis is of paramount importance