Piperlongumine (PPL), a natural plant product, has been extensively studied in cancer treatment going up on clinical trials. Since the first report related to its use on cancer research (in 2011) around 80 papers have been published in less than 10 years, but a gap still remaining. There are no metabolism studies of PPL in human organism. For the lack of a better view, here, the CYP450in vitrooxidation of PPL was described for the first time. In addition, the enzymatic kinetic data, the predictedin vivoparameters, the produced metabolites, the phenotyping study and possible piperlongumine-drug interactionsin vivois presented.

Rosuvastatin calcium (ROS), (Figure 1) belongs to the “statins” group, which is the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. This drug is indicated for dyslipidemias treatment and can help to decrease the level of “bad cholesterol” and can consequently reduce the development of atherosclerosis and the risk of heart diseases. ROS was developed by Astra-Zeneca and it was approved in 2003 by the FDA in the United States. In 2015, under the trade name Crestor®, it was the fourth largest selling drug in the United States with sales above $5 billion. This study presents a literature review of analytical methods for the quantification of ROS in pharmaceutical preparations and biological fluids. The major analytical methods described in this study for ROS were spectrophotometry, high-performance liquid chromatography (HPLC) coupled to ultraviolet (UV) detection, and tandem mass spectrometry (LC–MS/MS).

Chronic Chagas disease might have an impact on benznidazole pharmacokinetics with potential alterations in the therapeutic dosing regimen. The study aims to investigate the influence of chronic T. cruzi infection on the pharmacokinetics and biodistribution of benznidazole in mice. Healthy (n = 40) and chronically T. cruzi (Berenice-78 strain) infected (n = 40) Swiss female 10-month old mice received a single oral dose of 100 mg/kg benznidazole. Serial blood, heart, colon and brain samples were collected up to 12 h after benznidazole administration. The serum and tissues samples were analyzed using a High Performance Liquid Chromatography instrument coupled to a diode array detector. The chronic infection by T. cruzi increased the following pharmacokinetic parameter values Ka (3.92 vs 1.82 h⁻¹), Vd/F (0.089 vs 0.036 L) and CL/F (0.030 vs 0.011 liters/h), and reduced the values of Tmax (0.67 vs 1.17 h) and t _1/2a (0.18 vs 0.38 h). The tissue exposure (AUC_0-t,tissue) was longer and higher in the chronic infected mice in colon (8.15 vs 21.21 μg h/g) and heart (5.72 vs 13.58 μg h/g). The chronic infection also increased 1.6; 3.25 and 3 times of the benznidazole tissue penetration ratio (AUC_{0-t, tissue}/AUC_{0-t, serum}) of brain, colon and heart, respectively. The experimental chronic Chagas disease inflammation-mediated changes in the regulation of membrane transporters, probably influence the benznidazole pharmacokinetics and extent benznidazole exposure in the tissues. These results advise for potential alterations in benznidazole pharmacokinetics in chronic Chagas disease patients with possibilities of changes in the standard dosing regimen.

Piperlongumine is an amide alkaloid found in Piperaceae species that shows a broad spectrum of biological properties, including antitumor and antiparasitic activities. Herein, the leishmanicidal effect of piperlongumine and its derivatives produced by a biomimetic model using metalloporphyrins was investigated. The results showed that IC₅₀ values of piperlongumine in promastigote forms of Leishmania infantum and Leishmania amazonensis were 7.9 and 3.3 µM, respectively. The IC₅₀ value of piperlongumine in the intracellular amastigote form of L. amazonensis was 0.4 µM, with a selectivity index of 25. The piperlongumine biomimetic derivatives, Ma and Mb, also showed leishmanicidal effects. We also carried out an in vitro metabolic degradation study showing that Ma is the most stable piperlongumine derivative in rat liver microsome incubations. The results presented here indicate that piperlongumine is a potential leishmanicidal candidate and support the biomimetic approach for development of new antileishmanial derivatives.