Ex Vivo Evaluation of Intravaginal Progesterone and Testosterone to Treat the Luteal-phase Deficiency and Vaginal Atrophy.

The purpose of this study was to evaluate the transmucosal permeation of progesterone and testosterone using Pentravan as its vehicle for vaginal delivery. Progesterone deficiency is a hormone imbalance that could lead to luteal-phase deficiency, which is a common problem in assisted reproductive technologies. Testosterone has been explored for treating postmenopausal symptoms, such as vaginal atrophy. The ex vivo experiments were performed using porcine vaginal mucosa and phosphate buffered saline + 0.5% 2-hydroxypropyl-ß-cyclodextrin as the receptor media, which was later quantified through high-performance liquid chromatography. The percentage of the permeated drug was 0.4% and 20.3% for progesterone and testosterone, respectively. The permeation studies revealed that testosterone formulated with Pentravan is potentially effective in reaching the bloodstream and acts locally, whereas progesterone was mostly retained in the mucosa.

Insights about resveratrol analogs against trypanothione reductase of Leishmania braziliensis: Molecular modeling, computational docking and in vitro antileishmanial studies.

In this work, we combined molecular modeling, computational docking and in vitro analysis to explore the antileishmanial effect of some resveratrol analogs (ResAn), focusing on their pro-oxidant effect. The molecular target was the trypanothione reductase of Leishmania braziliensis (LbTryR), an essential component of the antioxidant defenses in trypanosomatid parasites. Three-dimensional structures of LbTryR were modeled and molecular docking studies of ResAn1-5 compounds showed the following affinity: ResAn1 > ResAn2 > ResAn4 > ResAn5 > ResAn3. Positive correlation was observed between these compounds' affinity to the LbTryR and the IC50 values against Leishmania sp (ResAn1 < ResAn2 < ResAn4), which allows for TryR being considered an important target for them. As the compound ResAn1 showed the best antileishmanial activity, and docking studies showed its high affinity for NADP binding site (NS) of TryR, plus having been able to induce ROS production in L. braziliensis promastigotes treated, ResAn1 probably occupies NS interfering in the electron transfer processes responsible for the catalytic reaction. The in silico prediction of ADMET properties suggests that ResAn1 may be a promising drug candidate with properties to cross biological membranes and high gastrointestinal absorption, not violating Lipinski's rules. Ultimately, the antileishmanial effect of ResAn can be associated with a pro-oxidant effect which, in turn, can be exploited as an antimicrobial agent. Communicated by Ramaswamy H. Sarma.