Towards Novel Antiplasmodial Agents-Design, Synthesis and Antimalarial Activity of Second-Generation β-Carboline/Chloroquine Hybrids.

As the resistance of to the existing antimalarials increases, there is a crucial need to expand the antimalarial drug pipeline. We recently identified potent antimalarial compounds, namely harmiquins, hybrids derived from the β-carboline alkaloid harmine and 4-amino-7-chloroquinoline, a key structural motif of chloroquine (CQ). To further explore the structure-activity relationship, we synthesised 13 novel hybrid compounds at the position -9 of the β-carboline ring and evaluated their efficacy in vitro against 3D7 and Dd2 strains (CQ sensitive and multi-drug resistant, respectively).

Multicomponent syntheses enable the discovery of novel quisinostat-derived chemotypes as histone deacetylase inhibitors.

In this study, we synthesized and evaluated novel histone deacetylase (HDAC) inhibitors derived from the clinical candidate quisinostat. A library of 16 compounds categorized in three novel chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. First, the compounds were evaluated for their activity against the Plasmodium falciparum strains 3D7 and Dd2, the main malaria-causing parasite, identifying compound 18b of the type C series as the most potent.

Targeting the IspE Enzyme.

The enzyme IspE in is considered an attractive drug target, as it is essential for parasite survival and is absent in the human proteome. Yet it still has not been addressed by a small-molecule inhibitor. In this study, we conducted a high-throughput screening campaign against the IspE enzyme.

Development of peptoid-based heteroaryl-decorated histone deacetylase (HDAC) inhibitors with dual-stage antiplasmodial activity.

Dynamics of epigenetic modifications such as acetylation and deacetylation of histone proteins have been shown to be crucial for the life cycle development and survival of Plasmodium falciparum, the deadliest malaria parasite. In this study, we present a novel series of peptoid-based histone deacetylase (HDAC) inhibitors incorporating nitrogen-containing bicyclic heteroaryl residues as a new generation of antiplasmodial peptoid-based HDAC inhibitors. We synthesized the HDAC inhibitors by an efficient multicomponent protocol based on the Ugi four-component reaction.

Evolution over the last 40 years of the assisted reproduction technologies in cattle - the Brazilian perspective I - timed artificial insemination.

The reproductive efficiency of the herd is correlated with higher productivity in livestock. Reproduction biotechniques, such as ovulation synchronization protocols, are important to optimize production and accelerate genetic profit in beef and dairy herds. The objective of this review is to describe the evolution over the last 40 years of the artificial insemination (AI) and the timed-AI (TAI) protocols in cattle from a Brazilian perspective.

Biochemical profile and oocyte quality of primiparous Bos indicus cows submitted to a timed artificial insemination protocol.

The objective of this study was to verify the causes of the lower response of primiparous Bos indicus cows to the ovulation synchronization protocol. Two experiments were performed to evaluate the biochemical profile, oocyte and follicular cell quality (Experiment 1) and pregnancy (Experiment 2). In Experiment 1, suckled primiparous (n = 24) and multiparous cows (n = 24) were submitted to ovum pick up (OPU).

Genetic Identification and Technological Potential of Indigenous Lactic Acid Bacteria Isolated from , a Traditional Portuguese Sausage.

is a naturally fermented meat sausage traditionally made in the Portuguese region of . Lactic acid bacteria (LAB) are the dominant microorganisms in and can endow it with various technological properties. This study aimed (1) to characterize technological features and in vitro antimicrobial activity of LAB isolated from , and (2) to reveal associations between such phenotypic characteristics and the isolates species identified through amplification and sequencing of the 16S ribosomal gene.

High Target Homology Does Not Guarantee Inhibition: Aminothiazoles Emerge as Inhibitors of .

In this study, we identified three novel compound classes with potent activity against , the most dangerous human malarial parasite. Resistance of this pathogen to known drugs is increasing, and compounds with different modes of action are urgently needed. One promising drug target is the enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) of the methylerythritol 4-phosphate (MEP) pathway for which we have previously identified three active compound classes against .

Is estradiol valerate an alternative to estradiol benzoate in promoting the synchronization of ovulation and timed artificial insemination in suckled Bos indicus beef cows?

The objective of the present study was to evaluate the effect of estradiol valerate administered at the beginning of the ovulation synchronization protocol on the pregnancy rate of Bos indicus cows. In the experiments, the following products from MSD, Sao Paulo, Brazil were used: estradiol valerate (EV), estradiol benzoate (EB), intravaginal progesterone device (P4), estradiol cypionate (EC), equine chorionic gonadotropin (eCG) and cloprostenol (PGF). In Experiment 1, Bos indicus cows (n=899) with a body condition score (BCS) of 2.

Synthesis, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins.

Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and . The hybrids were prepared from the corresponding amines by 1,1'-carbonyldiimidazole (CDI)-mediated synthesis. evaluation of the biological activity of the title compounds revealed two hit compounds.

Lactic acid bacteria from artisanal raw goat milk cheeses: technological properties and antimicrobial potential.

In cheese-making, a starter culture composed of adequately chosen lactic acid bacteria (LAB) may be suitable to ensure the rapid acidification of milk, improve textural and sensory characteristics, and avoid pathogen proliferation. In this work, 232 LAB isolates collected from artisanal goat's raw milk cheeses produced in Portugal were evaluated for their antimicrobial capacity (at 10 and 37°C), as well as their acidifying and proteolytic properties. Among the 232 isolates, at least 98% of those isolated in De Man- Rogosa-Sharpe (MRS) agar presented antagonism against , Typhimurium, or , whereas less than 28.

Unveiling Microbial Chemical Interactions Based on Metabolomics Approaches.

Microorganisms are ubiquitous in diverse habitats and studying their chemical interactions with the environment and comprehend its complex relations with both hosts and environment, are crucial for the development of strategies to control microbial diseases. This chapter discusses the importance of studying microorganisms with agricultural benefits, using specialized metabolites as examples. Herein we highlight the challenges and opportunities in utilizing microorganisms as alternatives to synthetic pesticides and fertilizers in agriculture.

Lost to follow-up of patients who received intravitreal anti-vascular endothelial growth factor therapy to treat four different retina disorders in an individual center in Brazil.

Objectives: To identify risk factors for loss to follow-up in periodic intravitreal anti-vascular endothelial growth factor injections for the treatment patients with diabetic macular edema, subretinal neovascularization, age-related macular degeneration, and retinal vein occlusion in a single eye center in São Paulo, Brazil.

Methods: This was a retrospective longitudinal study that gathered information from 992 patients who required intravitreal anti-vascular endothelial growth factor drugs over 6 months. The authors included age, eye disease, laterality, monthly income, distance, and payment mode as risk factors.

Design, synthesis and antiplasmodial evaluation of new amide-, carbamate-, and ureido-type harmicines.

Malaria, one of the oldest parasitic diseases, remains a global health threat, and the increasing resistance of the malaria parasite to current antimalarials is forcing the discovery of new, effective drugs. Harmicines, hybrid compounds in which harmine/β-carboline alkaloids and cinnamic acid derivatives are linked via an amide bond or a triazole ring, represent new antiplasmodial agents. In this work, we used a multiple linear regression technique to build a linear quantitative structure-activity relationship (QSAR) model, based on a group of 40 previously prepared amide-type (AT) harmicines and their antiplasmodial activities against erythrocytic stage of chloroquine-sensitive strain of P.

Quantification of Plasmodium falciparum HRP-2 as an alternative method to [H]hypoxanthine incorporation to measure the parasite reduction ratio in vitro.

In the absence of a highly efficacious vaccine, chemotherapy remains the cornerstone to control malaria morbidity and mortality. The threat of the emergence of parasites resistant to artemisinin-based combination therapies highlights the need for new antimalarial drugs ideally with superior properties. The killing rate reflects the speed of action of antimalarial drugs, which can be measured in vitro through the parasite reduction ratio (PRR) assay to shortlist interesting candidates.

Technologies Applied to the Mental Health Care of Pregnant Women: A Systematic Literature Review.

Objective:  This article aims to review the literature regarding the use of technologies to promote mental health for pregnant women. We seek to: understand the strategies that pregnant women use for mental health care. Also, we investigate the existence of scientific evidence that validates such practices.

Use of injectable progesterone to replace the intravaginal progesterone device on the ovulation synchronization protocol reduces the pregnancy rate in Bos indicus cows.

The aim of this study was to evaluate the effectiveness of using different doses of injectable progesterone (P4i) in a new ovulation synchronization protocol in place of progesterone (P4)-releasing intravaginal devices in Bos indicus cows. For this, three experiments were carried out. To determine the P4-release curve (Experiment 1), 55 Bos indicus cows were distributed into 5 experimental groups for the administration of different doses of P4i at D0 (P4i60, n = 11; P4i105, n = 11; P4i150, n = 11; P4i195, n = 11 and P4i240, n = 11) and submitted to the ovulation synchronization protocol (D0: P4i + EB; D8: PGF2α + EC + eCG).

The Implementation of an Integrated Oral Care Protocol for Pediatric Cancer Patients: a Qualitative Study.

Aim: In this study, we evaluated the impact of an integrated oral care protocol for pediatric patients undergoing antineoplastic treatment from the perspective of the multidisciplinary team, oral healthcare team, and caregivers.

Subject And Methods: This was a qualitative study carried out in the pediatric sector of a reference cancer hospital in Brazil. Focus group and individual semi-structured interview techniques were used, and the data were analyzed by the Discourse of the Collective Subject (DCS) method.

Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity.

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds.

Regio- and Stereoselective Epoxidation and Acidic Epoxide Opening of Antibacterial and Antiplasmodial Chlorotonils Yield Highly Potent Derivatives.

The rise of antimicrobial resistance poses a severe threat to public health. The natural product chlorotonil was identified as a new antibiotic targeting multidrug resistant Gram-positive pathogens and Plasmodium falciparum. Although chlorotonil shows promising activities, the scaffold is highly lipophilic and displays potential biological instabilities.

Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages of .

Boromycin is a boron-containing macrolide antibiotic produced by with potent activity against certain viruses, Gram-positive bacteria and protozoan parasites. Most antimalarial antibiotics affect plasmodial organelles of prokaryotic origin and have a relatively slow onset of action. They are used for malaria prophylaxis and for the treatment of malaria when combined to a fast-acting drug.

Secretome effect of adipose tissue-derived stem cells cultured two-dimensionally and three-dimensionally in mice with streptozocin induced type 1 diabetes.

Aims: To analyze therapeutic potential of the conditioned medium from adipose tissue-derived stem cells (ASC) cultivated in 2D (CM-2D) and 3D (CM-3D) models, in mice with Type 1 diabetes (T1D) induced by streptozotocin.

Main Methods: Viability andCD105 expression of 2D and 3D ASC were analyzed by flow cytometry. T1D was induced in mice by multiple injections of streptozocin.