Pharmacometabolomics Approach to Explore Pharmacokinetic Variation and Clinical Characteristics of a Single Dose of Desvenlafaxine in Healthy Volunteers.

This study investigated the effects of a single dose of desvenlafaxine via oral administration on the pharmacokinetic parameters and clinical and laboratory characteristics in healthy volunteers using a pharmacometabolomics approach. In order to optimize desvenlafaxine's therapeutic use and minimize potential adverse effects, this knowledge is essential. Thirty-five healthy volunteers were enrolled after a health trial and received a single dose of desvenlafaxine (Pristiq, 100 mg).

Kaempferol and Biomodified Kaempferol from Extract as Potential Sources of Anti-Cancer Polyphenolics against High Grade Glioma Cell Lines.

The enzymatic hydrolysis of the extract of by two glycosyl hydrolases (hesperidinase and galactosidase) was performed in order to obtain kaempferol (KPF)-enriched extract with an enhanced anticancer activity. The current study examined the effectiveness of both extracts (before (KPF-BBR) and after (KPF-ABR) bioconversion reactions) in reducing cell viability and inducing apoptosis in human high-degree gliomas in vitro. Cytotoxicity was determined using an MTT assay.

Urine Metabolites Enable Fast Detection of COVID-19 Using Mass Spectrometry.

The COVID-19 pandemic boosted the development of diagnostic tests to meet patient needs and provide accurate, sensitive, and fast disease detection. Despite rapid advancements, limitations related to turnaround time, varying performance metrics due to different sampling sites, illness duration, co-infections, and the need for particular reagents still exist. As an alternative diagnostic test, we present urine analysis through flow-injection-tandem mass spectrometry (FIA-MS/MS) as a powerful approach for COVID-19 diagnosis, targeting the detection of amino acids and acylcarnitines.

Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers.

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects.

Rapid Screening of COVID-19 Directly from Clinical Nasopharyngeal Swabs Using the MasSpec Pen.

The outbreak of COVID-19 has created an unprecedent global crisis. While the polymerase chain reaction (PCR) is the gold standard method for detecting active SARS-CoV-2 infection, alternative high-throughput diagnostic tests are of a significant value to meet universal testing demands. Here, we describe a new design of the MasSpec Pen technology integrated to electrospray ionization (ESI) for direct analysis of clinical swabs and investigate its use for COVID-19 screening.

Sensitive LC-MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies.

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC-MS/MS for rivaroxaban quantification in human plasma using an one-step liquid-liquid extraction.

Photoinactivation of different human tumor cell lines and sheep red blood cells in vitro by liposome-bound Zn(II) Phthalocyanine: Effects of cholesterol.

The in vitro photoinactivation of human tumor cell lines and sheep red blood cells (SRBC) by Zinc (II) Phthalocyanine (ZnPc) was investigated using unilamellar liposome (LUV) as delivery system, in the presence and absence of cholesterol (CHOL) in the formulation. The presence of CHOL improves the stability of the system showing to be essential for the photodynamic action of ZnPc. LUVs prepared without CHOL did not present any antiproliferative effects neither induced significant photohaemolysis.

Antineoplastic 31-norcycloartanones from Solanum cernuum vell.

Triterpenoids with 31-norcycloartanone structure were isolated for the first time from the Solanum genus. Cycloeucalenone and 24-oxo-31-norcycloartanone were the main constituents of the dichloromethane extract of Solanum cernuum Vell. leaves [7% (w/w) and 1.

Synthesis and differential antiproliferative activity of Biginelli compounds against cancer cell lines: Monastrol, oxo-monastrol and oxygenated analogues.

The synthesis and differential antiproliferative activity of monastrol (1a), oxo-monastrol (1b) and eight oxygenated derivatives 3a,b-6a,b on seven human cancer cell lines are described. For all evaluated cell lines, monastrol (1a) was shown to be more active than its oxo-analogue, except for HT-29 cell line, suggesting the importance of the sulfur atom for the antiproliferative activity. Monastrol (1a) and the thio-derivatives 3a, 4a and 6a displayed relevant antiproliferative properties with 3,4-methylenedioxy derivative 6a being approximately more than 30 times more potent than monastrol (1a) against colon cancer (HT-29) cell line.

(R)-Goniothalamin: total syntheses and cytotoxic activity against cancer cell lines.

The total syntheses of (R)-goniothalamin (1), a styryl lactone isolated from several Goniothalamus species, via catalytic asymmetric allylation of alpha-benzyloxyacetaldehyde (2), followed by ring-closing metathesis and Wittig olefination and via catalytic asymmetric allylation of trans-cinnamaldehyde (12), followed by ring-closing metathesis are reported. The antiproliferative activities of (R)-1 and its Z-isomer 10 as well as of the synthetic dihydropyranone intermediates 7 and 8 against eight different cancer cell lines are also described.

Enantioselective syntheses of (R)- and (S)-argentilactone and their cytotoxic activities against cancer cell lines.

Concise total syntheses of (R)- and (S)-argentilactone have been developed via enantioselective catalytic allylation (ECA) and ring-closing metathesis pathways (four steps, 39% overall yield and 82-84% ee) from 2-octynal and their in vitro activity against cancer cells is described.

A novel sunscreen agent having antimelanoma activity.

A novel series of eight dibenzoylmethane derivatives having both sunscreen and cytotoxic activity has been obtained by derivatizing commercial dibenzoyl methanes. Four human cancer cell lines (MCF 7 (breast), NCI ADR (breast expressing the multidrug resistance phenotype), NCI 460 (lung) and UACC 62 (melanoma)) were used for the cytotoxic assay. Eight among the 19 dibenzoylmethane derivatives showed cytotoxicity against these four cell lines.

Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua.

Artemisinin 1, dihydro-epideoxyarteannuin B 2 and deoxyartemisinin 3 were isolated from the sequiterpene lactone-enriched fraction obtained from the crude ethanolic extract of Artemisia annua L. These compounds were tested on ethanol and indomethacin-induced ulcer models. Compound 1 did not afford cytoprotection under the experimental models tested.