Current Medicinal Chemistry - Volume 25, Issue 30, 2018

Background: Research in the field of antitumor chemotherapeutics pursues a key issue, drug selectivity for cancer cells. In the last 20 years, a group of proteins has attracted scientific interest as cancer chemotherapeutics due to their ability to specifically kill cancer cells while leaving normal cells undamaged. One of these proteins is apoptin. Methods: In this study, the recent available literature regarding cell death mechanisms induced by apoptin has been reviewed. Delivering this drug to tumor cells is a challenge because it spontaneously forms soluble non-covalent aggregates. This led us to include in this review the different approaches for obtaining the maximum efficiency of apoptin entry to cancer cells. Results: This review provides an up-to-date summary of the mechanisms by which apoptin induces selective apoptosis in tumor cells while leaving normal cells undamaged. It highlights the relationship between the apoptosis mechanism induced by this protein and its functional motifs. Apoptin has been described as an intrinsically disordered protein, which explains its ability to interact with multiple partners and affect multiple pathways inside the cell. Characterization of the different partners and pathways induced by apoptin has begun to shed light on the molecular basis of apoptin's tumor-selective cytotoxicity. Conclusion: The findings confirm the interest in apoptin as a potentially safe antitumor drug. Research still needed to be conducted to find an effective way to deliver apoptin for use in clinics.

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels.

Background: Plant biofactories are biotechnological platforms based on plant cell and organ cultures used for the production of pharmaceuticals and biopharmaceuticals, although to date only a few of these systems have successfully been implemented at an industrial level. Metabolic engineering is possibly the most straightforward strategy to boost pharmaceutical production in plant biofactories, but social opposition to the use of GMOs means empirical approaches are still being used. Plant secondary metabolism involves thousands of different enzymes, some of which catalyze specific reactions, giving one product from a particular substrate, whereas others can yield multiple products from the same substrate. This trait opens plant cell biofactories to new applications, in which the natural metabolic machinery of plants can be harnessed for the bioconversion of phytochemicals or even the production of new bioactive compounds. Synthetic biological pipelines involving the bioconversion of natural substrates into products with a high market value may be established by the heterologous expression of target metabolic genes in model plants. Objective: To summarize the state of the art of plant biofactories and their applications for the pipeline production of cosme-, pharma- and biopharmaceuticals. Results: In order to demonstrate the great potential of plant biofactories for multiple applications in the biotechnological production of pharmaceuticals and biopharmaceuticals, this review broadly covers the following: plant biofactories based on cell and hairy root cultures; secondary metabolite production; biotransformation reactions; metabolic engineering tools applied in plant biofactories; and biopharmaceutical production.

Background: Adenosine is an endogenous purine nucleoside, which mediates a variety of important biological processes and diseases, such as vasodilation, inflammation, cancer, wound healing, ischemia reperfusion injury, Parkinson disease, infectious diseases, and other CNS disorders. Particularly important are the A2A receptors that have been expressed in the lung, liver, heart, cardiovascular tissues, leukocytes, neutrophils, and endothelial cells. This review provides an update of the latest A2A receptor agonists developed in the period 2005-2017, their selectivity regarding other adenosine receptors and their potential therapeutic applications. Methods: I have conducted an extensive search from the most common bibliographic databases for critically review the most recent works on the A2A receptor agonists and their therapeutic applications in inflammation, asthma and chronic obstructive pulmonary disease, myocardial perfusion imaging, sepsis, rheumatoid arthritis, and wound healing, among others. Results: In the last decade, a great deal of effort has been devoted to develop adenosine receptor agonists and antagonists for treatment of a number of diseases. Thus, for A2A receptor agonists more than 130 papers and reviews have been found, many of them highlighting the usefulness of these compounds in the field. Conclusions: Although so far many of the A2A receptor agonists have failed in clinical trials due to their side effects, some of them have been approved for protection against cardiac ischemia-reperfusion injury and anemia. The recently reported crystal structure of the human A2A receptor in complex with the agonist UK-432097 is a fundamental keystone for the development of new and selective A2A ligands with new therapeutic applications.

Bile acids or bile salts, belong to a large family of biological steroid derivatives found predominantly in the bile of mammals and other vertebrates. These amphipathic molecules possess numerous functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate catabolites, emulsifying fat-soluble vitamins to enable their absorption, aiding in motility and in reducing the bacteria flora found in the small intestine and biliary tract. In this review, we investigate progress towards synthetic bile acid derivatives, with special emphasis on how they might be used for various biological applications and the challenges that remain in developing these compounds as potent drugs of the future especially in the field of microbiology (antimicrobial activities) and cancer (anticancer agents). We will emphasize the fact that even few researches are devoted around these peculiar structures. All the researches pointed out the important potential of such derivatives for the design of new classes of drugs.

Leishmaniasis and Chagas disease are endemic pathologies in tropical countries. These cause high morbidity and a public health problem. Current chemotherapies are based on conventional drugs with variable efficacy and toxicity related with the length of therapeutic schemes and high doses. When two pharmacological agents are combined into a single molecule, the result is the so-called hybrid molecule. In the search for new treatments against Chagas disease and leishmaniasis, several studies have shown that hybrid molecules display high antiprotozoal activity and this emerging strategy is quite promising in the field of new drug discovery and development. This review focuses on the antiprotozoal activity of different hybrids obtained from the hybridization of pharmacophores, showing that the most of the efforts have been concentrated in the molecular hybridization of quinoline, chalcone and hydrazone moieties.