Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.

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Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good in vivo efficacy against Mycobacterium tuberculosis. Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.

Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1).

Chagas disease, also known as American trypanosomiasis, is one of the 17 neglected tropical diseases (NTDs) according to World Health Organization. It is estimated that 8-10 million people are infected worldwide, mainly in Latin America. Chagas disease is caused by the parasite Trypanosoma cruzi and is characterized by two phases: acute and chronic. The current therapy for Chagas disease is limited to drugs such as nifurtimox and benznidazole, which are effective in treating only the acute phase of the disease. In addition, several side effects ranging from hypersensitivity to bone marrow depression and peripheral polyneuropathy have been associated with these drugs. Therefore, the current challenge is to find new effective and safe drugs against this NTD. The aim of this review is to describe the advances in the medicinal chemistry of new anti-chagasic compounds reported in the literature in the last five years. We report promising prototypes for drug discovery identified through target-based and phenotype-based strategies and present some important targets for the development of new synthetic compounds.