Marine natural peptides: Determination of absolute configuration using liquid chromatography methods and evaluation of bioactivities

Over the last decades, many naturally occurring peptides have attracted the attention of medicinal chemists due to their promising applicability as pharmaceuticals or as models for drugs used in therapeutics. Marine peptides are chiral molecules comprising different amino acid residues. Therefore, it is essential to establish the configuration of the stereogenic carbon of their amino acid constituents for a total characterization and further synthesis to obtain higher amount of the bioactive marine peptides or as a basis for structural modifications for more potent derivatives. Moreover, it is also a crucial issue taking into account the mechanisms of molecular recognition and the influence of molecular three-dimensionality in this process. In this review, a literature survey covering the report on the determination of absolute configuration of the amino acid residues of diverse marine peptides by chromatographic methodologies is presented. A brief summary of their biological activities was also included emphasizing to the most promising marine peptides. A case study describing an experience of our group was also included. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.This research was partially supported by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF), in the framework of the programme PT2020, the project PTDC/MAR-BIO/4694/2014 (reference POCI-01-0145-FEDER-016790; Project 3599—Promover a Produção Científica e Desenvolvimento Tecnológico e a Constituição de Redes Temáticas (3599-PPCDT)) as well as by the project INNOVMAR— Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01- 0145-FEDER-000035, within Research Line NOVELMAR), supported by North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the Europeann Regional Development Fund (ERDF), and Chiral_Drugs_CESPU_2017. Phyo thanks the Erasmus Mundus Action 2 (Lotus Plus project) for a PhD’s scholarship

Impact of the admitting ward on care quality and outcomes in non-ST-segment elevation myocardial infarction (NSTEMI) : insights from a national registry

Peer reviewedPostprin

Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine:A potential role for homoserine kinase in insect-stage Trypanosoma brucei

10.1111/mmi.12853Molecular Microbiology951143-15

Meta-Analysis of the Prognostic Impact of Anemia in Patients Undergoing Percutaneous Coronary Intervention

This study was funded by an award from the North Staffordshire Medical Institute, Stoke-on-Trent, United Kingdom.Peer reviewedPostprin

Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection were randomized (1:1) to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. CONCLUSION: Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. TRIAL REGISTRATION: Clinicaltrials.gov NCT00440999

Opsonising antibodies to P. falciparum Merozoites associated with immunity to clinical malaria

Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the precise mechanisms remain unclear. Although antibody levels can be measured by ELISA, few studies have investigated functional antibody assays in relation to clinical outcomes. In this study we applied a recently developed functional assay of antibody-mediated opsonisation of merozoites, to plasma samples from a longitudinal cohort study conducted in a malaria endemic region of Papua New Guinea (PNG). Phagocytic activity was quantified by flow cytometry using a standardized and high-throughput protocol, and was subsequently evaluated for association with protection from clinical malaria and high-density parasitemia. Opsonising antibody responses were found to: i) increase with age, ii) be enhanced by concurrent infection, and iii) correlate with protection from clinical episodes and high-density parasitemia. Stronger protective associations were observed in individuals with no detectable parasitemia at baseline. This study presents the first evidence for merozoite phagocytosis as a correlate of acquired immunity and clinical protection against P. falciparum malaria