QT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection.

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements.

Design and synthesis of simplified speciophylline analogues and β-carbolines as active molecules against Plasmodium falciparum.

A structure-activity relationship study of active molecules against chloroquine-resistant Plasmodium falciparum K1 strain is reported. Structurally simplified analogues of antiplasmodial active alkaloids presented similar levels of activity as their corresponding natural products extracted from Guiera senegalensis and Mitragyna inermis with IC values on chloroquine-resistant P. falciparum K1 strain of up to 10.

Prescription errors related to the use of computerized provider order-entry system for pediatric patients.

Objectives: To evaluate the nature and frequency of medication errors resulting from the use of a computerized provider order-entry (CPOE) system in a pediatric department.

Methods: We conducted a retrospective study to examine errors related to computerized orders using the software Pharma (Computer Engineering, France) in pediatric department between 31/05/2015 to 01/12/2015. These errors were signaled by pharmacists who examine CPOEs daily.

Chemical profiling of the tuber of Stephania cambodica Gagnep. (Menispermaceae) and analytical control by UHPLC-DAD.

A new aporphine glycoside (1), named 'angkorwatine', and eight known alkaloids: oblongine (2), stepharine (3), asimilobine-β-d-glucopyranoside (4), isocorydine (5), tetrahydropalmatine (THP) (6), jatrorrhizine (7), palmatine (PAL) (8), and roemerine (ROE) (9) were simultaneously isolated from the tuber of Stephania cambodica. The development and validation of UHPLC-DAD method was carried out for the quantification of marker compounds (PAL, ROE, THP) of S. cambodica.

Chemical Composition, Antioxidant and Cytotoxic Activities of Roots and Fruits of Berberis libanotica.

Fourteen compounds belonging to different chemical classes were characterized in the roots and fruits extracts from Berberis libanotica, using the same HPLC-DAD-MS method. Thirteen were reported, for the first time, from the fruits whereas the roots contained mostly alkaloids of which 3 out of 5 are reported for the first time. Their structures were established on the basis of MS data as gallic acid (1), chlorogenic acid (2), delphinidin (3), oxyacanthine (4), rutin (5), hyperoside (6), berbamine (7), isoquercitrin (8), quercitrin (9), jatrorrhizine (10), palmatine (11), berberine (12), quercetin (13) and luteolin (14).

Ethnobotany, phytochemistry and pharmacology of Stephania rotunda Lour.

Ethnopharmacological Relevance: Stephania rotunda Lour. (Menispermaceae) is an important traditional medicinal plant that is grown in Southeast Asia. The stems, leaves, and tubers have been used in the Cambodian, Lao, Indian and Vietnamese folk medicine systems for years to treat a wide range of ailments, including asthma, headache, fever, and diarrhoea.

In vitro cytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated from Cyclamen persicum and Cyclamen libanoticum.

Context: The genus Cyclamen L. (Primulaceae) is rich in saponins known to have interesting biological activities.

Objective: To isolate saxifragifolin B and cyclamin, two triterpene saponins, from Cyclamen libanoticum Hildebr and Cyclamen persicum Mill, and to assess their cytotoxic, clastogenic/aneugenic, and anticlastogenic effects, as well as antioxidant potential.

Cytotoxic withanolides from the leaves of Moroccan Withania frutescens.

Context: Withania species are a rich source of interesting phytochemical substances (withanolides) which have shown several biological properties.

Objective: To investigate the cytotoxic potential of Withania frutescens (L.) Pauquy (Solanaceae) leaf extracts and isolated active compounds against cultured tumor cell lines.

HPLC analysis and cytotoxic activity of Vernonia cinerea.

The extracts of five Cambodian medicinal plants (Aganosma marginata, Dracaena cambodiana, Harrisonia perforata, Hymenodictyon excelsum and Vernonia cinerea) were evaluated in vitro for their cytotoxic activity against HT29 colon adenocarcinoma cells and HepG2 hepatoma cells, using the MTT assay. Among these five plants, Vernonia cinerea displayed potent cytotoxicity. One main sesquiterpene lactone, 8alpha-tigloyloxy-hirsutinolide-13-O-acetate was isolated from the whole plant of V.

New antiplasmodial alkaloids from Stephania rotunda.

Ethnopharmacological Relevance: Stephania rotunda Lour. (Menispermaceae) is a creeper growing in many countries of Asia and commonly found in the mountainous areas of Cambodia. As a folk medicine, it has been mainly used for the treatment of fever and malaria.

HPLC analysis of Stephania rotunda extracts and correlation with antiplasmodial activity.

Stephania rotunda (Menispermaceae), a creeper commonly found in the mountainous areas of Cambodia, has been mainly used for the treatment of fever and malaria. Thus, the aim of this study is to investigate the chemical composition and antiplasmodial activity of different samples of S. rotunda and compare their antiplasmodial activity with their alkaloid content.

Chionanthus virginicus L.: phytochemical analysis and quality control of herbal drug and herbal preparations.

Root barks of Chionanthus virginicus L. are used in homeopathic medicines in the treatment of icterus and hepatitis. The objective of this study is to identify novel secoiridoids and lignans and to develop a simple and reliable HPLC method for the determination of oleuropein, phillyrin, total secoiridoids and total lignans for quality control and stability studies of C.

Antiplasmodial activity of three bisbenzylisoquinoline alkaloids from the tuber of Stephania rotunda.

Three bisbenzylisoquinoline alkaloids were isolated for the first time from Stephania rotunda tuber. Their structures were elucidated by spectroscopic methods and their antiplasmodial activity was investigated in vitro on chloroquine resistant Plasmodium falciparum strain W2. These alkaloids were identified as 2-norcepharanthine (1), cepharanoline (2) and fangchinoline (3).

Simultaneous HPLC determination of three bioactive alkaloids in the Asian medicinal plant Stephania rotunda.

A reliable high-performance liquid chromatography (HPLC) method coupled with photodiode array detection has been developed and validated for the determination of three major alkaloids: cepharanthine, tetrahydropalmatine and xylopinine in Stephania rotunda Lour. (Menispermaceae) collected in Cambodia. The chromatographic separation was carried out on a Symmetry C8 column (250 mm x 4.

New triterpenoid saponins from Leontice smirnowii.

Three new triterpene saponins, leonticins I (1), J (2) and L (3) were isolated from the tubers of Leontice smirnowii. On the basis of spectroscopic methods, including 2D NMR experiments (DEPT, gs-COSY, gs-HMQC, gs-HMBC and gs-HSQC-TOCSY), mass spectrometry (HR-ESI-MS) and chemical degradation, the structures of the new compounds were elucidated as 3-O-β-D-glucopyranosyl-(1 → 3)-[β-D-xylopyranosyl-1 → 2)]-α-L-arabinopyranosyl-28-O-[α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl]-3β-hydroxy-30-norolean-12,20(29)-dien-28-oic acid (1), 3-O-[β-D-xylopyranosyl-(1 → 3)-β-D-galactopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 3)-α-L-arabinopyranosyl]-28-O-[α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl]-3β-hydroxy-30-norolean-12,20(29)-dien-28-oic acid (2) and 3-O-[β-D-xylopyranosyl-(1 → 3)-β-D-galactopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 3)]-[β-D-xylopyranosyl-(1 → 2)]-α-L-arabinopyranosyl]-28-O-[α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl]-3β-hydroxy-30-norolean-12,20(29)-dien-28-oic acid (3), respectively. The aglycone 3β-hydroxy-30-norolean-12,20(29)-dien-28-oic acid was observed for the first time in Leontice species.

Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected].

Three major alkaloids: cepharanthine (1), tetrahydropalmatine (2) and xylopinine (3) isolated from Stephania rotunda tuber were investigated for their cytotoxic activity in a panel of human cancer cells (HT29, LS174T, SW620 and HepG2) using MTT assay. In the present study, cepharanthine (1) exerted potent cytotoxicity against colon and hepatoma cancer cell lines with IC(50) values between 2.4 and 5.

Alpha-hederin potentiates 5-FU antitumor activity in human colon adenocarcinoma cells.

The aim of this study was to investigate the ability of alpha-hederin to improve the efficacy of widely prescribed 5-fluorouracil (5-FU) in a human colon adenocarcinoma model. Drug combinations of alpha-hederin and 5-FU using both fixed-concentration and combination index methods were performed in vitro in HT-29 cells. The results showed that alpha-hederin at sub-IC(50) cytotoxic concentrations enhanced 5-FU cytotoxicity about 3.

In vitro antimicrobial activity of plants used in Cambodian traditional medicine.

The purpose of the present study was to screen 27 plant species used in the traditional medicine of Cambodia for in vitro antibacterial and antifungal activities. Thirty-three methanolic extracts were tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Mycobacterium smegmatis and Candida albicans. Screened by disk diffusion assay, the extracts showed antimicrobial activity especially on Gram-positive bacteria.

Antimalarial activity of alkaloids isolated from Stephania rotunda.

Stephania rotunda (Menispermaceae) is used in traditional medicine for the treatment of fever. Four major alkaloids: dehydroroemerine, tetrahydropalmatine, xylopinine, cepharanthine as well as aqueous extract (SA), dichloromethane extracts (SD1 and SD2) from this plant were tested against Plasmodium falciparum W2 in vitro. Dehydroroemerine, cepharanthine and SD1 were the most active against W2 with IC(50) of 0.

Inter-species variability of haplamine metabolism and identification of its phase I metabolites from liver microsomes.

Haplamine, a pyranoquinoline alkaloid, was isolated from the genus Haplophyllum. The inter-species variability of haplamine metabolism was determined by reversed phase high performance liquid chromatography (HPLC) with UV detection. Microsomes from the liver of rats, mice, rabbits, guinea-pigs and humans were incubated with haplamine.

Screening of selected indigenous plants of Cambodia for antiplasmodial activity.

The in vitro antiplasmodial activity of 117 aqueous, methanol and dichloromethane extracts derived from different parts of 28 indigenous wild plant species was studied. These plants are commonly used in Cambodian traditional medicine. The plant extracts were tested for in vitro activity against a chloroquine resistant Plasmodium falciparum strain (W2).

Effect of several compounds on biliary excretion of paclitaxel and its metabolites in guinea-pigs.

The objective of this study was to evaluate the in vivo metabolic profile of paclitaxel and to examine the effect of potential co-administered drugs on the biliary secretion of paclitaxel and its metabolites in guinea-pigs. We first investigated in vitro paclitaxel metabolism using liver microsomes obtained from various species to identify the most suitable animal model with a similar metabolism to humans. Then, in vivo paclitaxel metabolism was investigated in male guinea-pigs.

Interspecies variability and drug interactions of loxapine metabolism in liver microsomes.

Loxapine is a dibenzoxazepine neuroleptic that is metabolized by the liver in humans. In the present study, we investigated first in vitro loxapine metabolism in liver microsomes from various species including rats, mice, guinea pigs, dogs, rabbits, monkeys and humans. This enables us to choose between species to further validate drug-drug interaction studies.

Population pharmacokinetics of etoposide: application to therapeutic drug monitoring.

Antineoplastic agent etoposide (VP16) displays narrow therapeutic index and erratic pharmacokinetics, and dose individualization is a convenient way for overcoming the interpatient variability, so as to maintain the drug exposure within a therapeutic range. The authors proposed a population-based Bayesian methodology to adjust routinely VP16 dosage when given as a 5-day infusion. The mean VP16 pharmacokinetic parameters of the reference population calculated from 14 patients following the two-stage method were CL = 1.