174Current Topics in Medicinal Chemistry, 2019, Vol. 19, No. 3 Perspectives in Medicinal Chemistry PERSPECTIVES IN MEDICINAL CHEMISTRY Leishmaniasis and Chagas Disease – Neglected Tropical Diseases: Treatment Updates Leandro Stefano Sangenito 1 , Vanessa da Silva Santos 1 , Claudia Masini d’Avila-Levy 2 , Marta Helena Branquinha 1 , André Luis Souza dos Santos 1,3,* and Simone S.C. de Oliveira 1 1 Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Ge- ral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; 2 Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janei- ro, Brazil; 3 Programa de Pós-Graduação em Bioquímica, Instituto de Química, Universidade Federal do Rio de Janei- ro, Rio de Janeiro, Brazil 1. INTRODUCTION The World Health Organization (WHO) [1] has listed 20 neglected tropical diseases (NTDs), including infections caused by viruses, bacteria, fungi and protozoa. Together, these illnesses put at risk more than 1.4 billion people that live in absolute pov- erty, primarily in developing countries. Despite the high morbidity and high costs with treatment/hospitalization, it is been evi- dent that the private sector does not have suitable interest in financing programs against many of the NTDs. This regrettable fact occurs because these conditions affect a portion of the population living on the margins of poverty, and therefore little fi- nancial return is obtained by the development of new drugs and diagnostic tests. This market strategy contributes to spread poverty and generates social stigma in this neglected population [1, 2]. Two of the most relevant NTDs include leishmaniasis and Chagas disease. Leishmaniasis is endemic in approximately 98 countries, especially those located in Latin America, East Africa and Southeast Asia, with 14 million people directly affected by the disease. By far, visceral leishmaniasis, or kala-azar, is the most important form because it causes the most severe disease, with 200-400 thousand cases per year and mortality estimated at 10–20%. Chagas disease, or American trypanosomiasis, is endemic in Latin America countries, affecting chronically approximately 6-7 million people and causing 14 thousand annual deaths. Both parasite infections have a common and severe problem: few alternative treatments are available to be used in clini- cal settings. The current treatment for both diseases has doubtful efficacy and requires continuous monitoring. Beyond the questionable efficacy, only a small portion of the infected population has access to the treatment. Moreover, the clinically ap- proved compounds are expensive and extremely toxic, causing several side effects due to the necessity of long-term administra- tion, which generates another global concern: the emergence of resistant strains [3, 4]. Therefore, this editorial aims to present the current treatment, the innovations in therapeutics and novel or “rediscovered” possible candidates against both neglected conditions, leishmaniasis and Chagas disease. 2. LEISHMANIASIS Currently available medications for the treatment of leishmaniasis have serious limitations, such as high cost, route of ad- ministration, side effects and increased resistance [3]. In this sense, a growing effort in the search for new anti- Leishmania che- motherapeutics has been observed over the last years using different approaches. These studies are focused on identifying short- term treatment strategies, including combination therapy, the search for new drug formulations as well as repositioning drugs [5]. Combined drug therapy is one of the strategies in the management of leishmaniasis that has been extensively explored in the treatment and clinical screening, seeking an increase in the effectiveness of drugs and a reduction in the time of treatment, besides the reduction of the toxic effects, since drugs may be used below their toxic doses [3, 5]. In this context, different clini- cal screening trials using combination therapy have been applied in the treatment of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) in different geographic regions where the disease is endemic, presenting good results when compared to the monotherapy. For instance, in Bihar (India), a study compared the efficacy of three treatment regimens: (i) single dose of AmBisome ® (a liposomal amphotericin B formulation), (ii) associated administration of miltefosine and paromomycin and (iii) AmBisome ® plus miltefosine concomitantly administered. The results revealed that all three treatments had acceptable out- comes and they were considered safe [6]. A study conducted in Bangladesh showed that the treatment of patients with VL using *Address correspondence to this author at the Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Tel.: +55 21 39380366; E-mail: andre@micro.ufrj.br 1873-4294/19 $58.00+.00 © 2019 Bentham Science Publishers