Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen “Neglected Tropical Diseases” (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Molecular Hybridization is an approach in rational drug design where new chemical entities are obtained by combining two or more pharmacophoric units from different bioactive compounds into a single molecule. Through this approach, medicinal chemists hope that the new hybrid derivative presents: better affinity and efficacy when compared to the parent drugs; a modified selectivity profile with improvement over pharmacokinetic and pharmacodynamic restrictions; dual or multiple modes of action; reduction of undesirable side effects; decreases in drug-drug interactions; reduced emergence or spread of drug resistance in microorganisms and protozoans; and lower cost. The approach has been successfully used by many research groups around the world and has had very promising results with diseases having multifactorial profiles, like Alzheimer´s, Parkinson´s disease, cancer, inflammation, and hypertension among others. The purpose of this paper is to conduct an updated review of molecular hybridization and multitarget profiling (a rational drug design approach), and its applications to the design and discovery of novel hybrid compounds with anti-inflammatory, antimicrobial, anticancer and antiprotozoal (leishmaniasis, malaria, and schistosomiasis) activities over the last six years.

Cancer is a life-threatening disease killing millions of people globally. Among various medical treatments, nano-medicines are gaining importance continuously. Many nanocarriers have been developed for treatment, but polymerically-based ones are acquiring importance due to their targeting capabilities, biodegradability, biocompatibility, capacity for drug loading and long blood circulation time. The present article describes progress in polymeric nano-medicines for theranostic cancer treatment, which includes cancer diagnosis and treatment in a single dosage form. The article covers the applications of natural and synthetic polymers in cancer diagnosis and treatment. Efforts were also made to discuss the merits and demerits of such polymers; the status of approved nano-medicines; and future perspectives.

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

Neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, are understood as occurring through genetic, cellular, and multifactor pathophysiological mechanisms. Several natural products such as flavonoids have been reported in the literature for having the capacity to cross the blood‐brain barrier and slow the progression of such diseases. The present article reports on in silico enzymatic target studies and natural products as inhibitors for the treatment of Parkinson’s and Alzheimer’s diseases. In this study we evaluated 39 flavonoids using prediction of molecular properties and in silico docking studies, while comparing against 7 standard reference compounds: 4 for Parkinson’s and 3 for Alzheimer’s. Osiris analysis revealed that most of the flavonoids presented no toxicity and good absorption parameters. The Parkinson’s docking results using selected flavonoids as compared to the standards with four proteins revealed similar binding energies, indicating that the compounds 8‐prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, capensinidin, and rosinidin are potential leads with the necessary pharmacological and structural properties to be drug candidates. The Alzheimer’s docking results suggested that seven of the 39 flavonoids studied, being those with the best molecular docking results, presenting no toxicity risks, and having good absorption rates (8‐prenylnaringenin, europinidin, epicatechin gallate, homoeriodictyol, aspalathin, butin, and norartocarpetin) for the targets analyzed, are the flavonoids which possess the most adequate pharmacological profiles.