Multitarget Compounds for Neglected Diseases: A Review.

Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety. Thus, the objective of our study is to evaluate existing multi-target compound approaches for neglected diseases, with an emphasis on Leishmaniasis, Chagas Disease, and Arboviruses. A literature review was performed by searching the database "Web of Sciences". In relation to the diseases covered in this work, Leishmaniasis, individually, was the one that presented the largest number of articles (11) that dealt with the topic, which can be justi-fied by the high prevalence of this disease in the world, the second most common disease was Dengue, followed by Chagas disease, Chikungunya virus, and Zika virus. Furthermore, the multi-target potential of phenolic compounds was observed in all diseases under study, with the mecha-nisms related to the nucleus and transcription being the most reported mechanisms. From this per-spective, it is worth highlighting the effectiveness of approaches related to multitarget drugs in discovering new therapeutic agents for neglected diseases.

Study on Morphological Changes and Interference in the Development of Aedes aegypti Caused by Some Essential Oil Constituents.

Dengue, Chikungunya and Zika are arboviruses, transmitted by the mosquito Aedes aegypti, that cause high mortality and serious health consequences in human populations. Efforts to control Ae. aegypti are important for preventing outbreaks of these diseases. Essential oil constituents are known to exhibit many activities, such as their use as larvicides. Given their potential, the present study aimed to characterize the larvicidal effect of dihydrojasmone, p-cymene, carvacrol, thymol, farnesol and nerolidol on the larvae of Ae. aegypti and their interference over the morphology of the mosquitos. The essential oil constituents were dissolved in dimethylsulfoxide at concentrations of 1-100 µg/mL and were applied in the breeding environment of third-stage larvae. The larvae from bioassays were fixed, dehydrated and embedded. Ultrathin sections were contrasted using 5% uranyl acetate and 1% lead citrate for observation through transmission electron microscopy. The oil with the highest larvicidal efficiency was found to be nerolidol, followed by farnesol, p-cymene, carvacrol, thymol and dihydrojasmone, with an LC50 of 11, 21, 23, 40, 45 and 66 µg/mL, respectively. The treated Ae. aegypti larvae caused alteration to the tegument or internal portions of larvae. The present study demonstrated which of these oils-dihydrojasmone, farnesol, thymol, p-cymene, carvacrol and nerolidol-have effective larvicidal activity.