The Design of Multi-target Drugs to Treat Cardiovascular Diseases: Two (or more) Birds on One Stone.

Cardiovascular diseases (CVDs) comprise a group of diseases and disorders of the heart and blood vessels, which together are the number one cause of death worldwide, being associated with multiple genetic and modifiable risk factors, and that may directly arise from different etiologies. For a long time, the search for cardiovascular drugs was based on the old paradigm "one compound - one target", aiming to obtain a highly potent and selective molecule with only one desired molecular target. Although historically successful in the last decades, this approach ignores the multiple causes and the multifactorial nature of CVDs.

Antiprotozoal agents: How have they changed over a decade?

Neglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical zones. The number and availability of drugs for treating these diseases are low, the administration route is inconvenient in some cases, and most of them have safety, efficacy, or adverse/toxic reaction issues. The need for developing new drugs to deal with these issues is clear, but one of the most drastic consequences of this negligence is the lack of interest in the research and development of new therapeutic options among major pharmaceutical companies.

The long and winding road of designing phosphodiesterase inhibitors for the treatment of heart failure.

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes known to play a critical role in the indirect regulation of several intracellular metabolism pathways through the selective hydrolysis of the phosphodiester bonds of specific second messenger substrates such as cAMP (3',5'-cyclic adenosine monophosphate) and cGMP (3',5'-cyclic guanosine monophosphate), influencing the hypertrophy, contractility, apoptosis and fibroses in the cardiovascular system. The expression and/or activity of multiple PDEs is altered during heart failure (HF), which leads to changes in levels of cyclic nucleotides and function of cardiac muscle. Within the cardiovascular system, PDEs 1-5, 8 and 9 are expressed and are interesting targets for the HF treatment.

Multicomponent Reactions for the Synthesis of Bioactive Compounds: A Review.

Multicomponent reactions (MCRs) are composed of three or more reagents in which the final product has all or most of the carbon atoms from its starting materials. These reactions represent, in the medicinal chemistry context, great potential in the research for new bioactive compounds, since their products can present great structural complexity. The aim of this review is to present the main multicomponent reactions since the original report by Strecker in 1850 from nowadays, covering their evolution, highlighting their significance in the discovery of new bioactive compounds.

Novel Quinolinyl-pyrrolo[3,4-d]pyrimidine-2,5-dione Derivatives Against Chloroquine-resistant Plasmodium falciparum.

Introduction: In this work DHPMs were combined with the quinoline nucleus to obtain new quinolinyl-pyrrolo[3,4-d]pyrimidine-2,5-dione compounds with improved antiplasmodial activity as well as decreased cytotoxicity. Nineteen quinolinyl-pyrrolo[3,4-d]pyrimidine-2,5-dione derivatives connected by a linker group to quinolone ring moieties with different substituents were synthesized and assayed against P. falciparum.

Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[3,4-d]-pyrimidinodiones as new antiplasmodial compounds.

BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial.

Discovery of a Series of Acridinones as Mechanism-Based Tubulin Assembly Inhibitors with Anticancer Activity.

Microtubules play critical roles in vital cell processes, including cell growth, division, and migration. Microtubule-targeting small molecules are chemotherapeutic agents that are widely used in the treatment of cancer. Many of these compounds are structurally complex natural products (e.

Conformational characterization of ipomotaosides and their recognition by COX-1 and 2.

The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility.

Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic saponin, through a molecular simplification of the carbohydrate moiety.

Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural products found in the Liquorice (Glycyrrhiza glabra L.) root extract. This saponin is known for its in vitro and in vivo thrombin inhibitory activity.

Synthesis and in vitro activity of limonene derivatives against Leishmania and Trypanosoma.

The synthesis and in vitro activity of R(+)-Limonene derivatives against Leishmania and Trypanosoma cruzi strains are reported. Seven compounds have shown better in vitro activity against Leishmania (V.)braziliensis than the standard drug pentamidine.

Synthesis of limonene beta-amino alcohol derivatives in support of new antileishmanial therapies.

A series of seven limonene beta-amino alcohol derivatives has been regioselectively synthesised in moderate to good yields. Two of these compounds were found to be significantly effective against in vitro cultures of the Leishmania (Viannia) braziliensis promastigote form in the micromolar range. The activities found for 3b and 3f were about 100-fold more potent than the standard drug, Pentamidine, in the same test, while limonene did not display any activity.