Unveiling the Targets Involved in the Quest of Antileishmanial Leads Using In silico Methods.

BACKGROUND: Leishmaniasis is a neglected tropical disease associated with several clinical manifestations, including cutaneous, mucocutaneous, and visceral forms. As currently available drugs have some limitations (toxicity, resistance, among others), the target-based identification has been an important approach to develop new leads against leishmaniasis. The present study aims to identify targets involved in the pharmacological action of potent antileishmanial compounds. METHODS: The literature information regarding molecular interactions of antileishmanial compounds studied over the past half-decade is discussed. The information was obtained from databases such as Wiley, SciFinder, Science Direct, National Library of Medicine, American Chemical Society, Scientific Electronic Library Online, Scopus, Springer, Google Scholar, Web of Science, etc. Results: Numerous in vitro antileishmanial compounds showed affinity and selective interactions with enzymes such as arginase, pteridine reductase 1, trypanothione reductase, pyruvate kinase, among others, which are crucial for the survival and virulence of the Leishmania parasite. CONCLUSION: The in-silico activity of small molecules (enzymes, proteins, among others) might be used as pharmacological tools to develop candidate compounds for the treatment of leishmaniasis. As some pharmacologically active compounds may act on more than one target, additional studies of the mechanism (s) of action of potent antileishmanial compounds might help to better understand their pharmacological action. Also, the optimization of promising antileishmanial compounds might improve their biological activity.

Flavones as a Privileged Scaffold in Drug Discovery: Current Developments.

BACKGROUND: Flavones are one of the main subclasses of flavonoids with diverse pharmacological properties. They have been reported to possess antimalarial, antimicrobial, anti-tuberculosis, anti-allergic, antioxidant, anti-inflammatory activities, among others. OBJECTIVE: The present review summarizes the recent information on the pharmacological properties of naturally occurring and synthetic flavones. METHODS: Scientific publications referring to natural and synthetic flavones in relation to their biological activities were hand-searched in databases such as SciFinder, PubMed (National Library of Medicine), Science Direct, Wiley, ACS, SciELO, Springer, among others. RESULTS: As per the literature, seventy-five natural flavones were predicted as active compounds with reference to their IC50 (<20 µg/mL) in in vitro studies. Also, synthetic flavones were found active against several diseases. CONCLUSION: As per the literature, flavones are important sources for the potential treatment of multifactorial diseases. However, efforts toward the development of flavone-based therapeutic agents are still needed. The appearance of new catalysts and chemical transformations is expected to provide avenues for the synthesis of unexplored flavones, leading to the discovery of flavones with new properties and biological activities.