Investigational drugs for visceral leishmaniasis

Abstract

Introduction The armamentarium of antileishmanials is small. It is further being threatened by development of resistance and decreasing sensitivity to the available drugs. Development of newer drugs are sorely needed. Areas covered Literature search on investigational drugs for visceral leishmaniasis (VL) was done on PubMed. Those candidates with at least in vitro and in vivo activity against leishmania species causing VL were reviewed. Among the investigational drugs the nitroimidazole compound fexinidazole is the one of the few drugs which has reached phase II trials. Although the (S)-PA-824 is in phase II trials for the treatment of tuberculosis its R enantiomer has shown good antileishmanial activity. Development of sitamaquin, which has completed phase II studies has been stopped for VL due to its low efficacy. Many novel delivery system and oral formulations of Amphotericin B which are cheap and less toxic are in investigational stages, and will go a long way in improving the treatment of VL. Expert opinion Very few new drugs have reached the clinical stage in the treatment of this neglected tropical disease. Thus, there is an urgent need for support from public private partnerships to ensure that drug candidates are promptly taken forward into development.

The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi

“…Currently, several investigations are being conducted to search for alternative treatments for leishmaniases [5] because of the small number of available drugs and the development of resistance or decreased sensitivity of parasite strains to existing treatments that are utilized for human therapy [5]. These studies have sought new methods and targets for diagnosis, new vaccine candidates and new rationally designed drugs that can be applied not only in humans, but also in dogs because canines are considered the major reservoirs of several species of Leishmania in the home environment and outdoors [6,7].…”

(+)-Spectaline, a Piperidine Alkaloid from <i>Senna spectabilis</i> DC. Effective in Reducing the <i>In Vitro</i> Infection of <i>Leishmania major</i>

“…Infrared spectrum was obtained using FTIR spectrometer and LCMS-QTOF. 1 H NMR (400 MHz) and 13 C NMR (100 MHz) spectra were recorded on a Bruker Avance 400 spectrometer, with deuterated chloroform (CDCl 3 ) as the solvent and tetramethylsilane (TMS) as internal standard. COSY, DEPT, HMQC and HMBC NMR experiments were performed on the same spectrometer.…”

“…These activities have been attributed to the flavonoids, phenylpropanoids, steroids, quinones, chalcones and a few more, but the most listed in reviews are alkaloids and terpenes [10,12].To date, a list of compounds from plants which have entered investigational stage had been summarized by Sundar and Chakravarty [13] which includes amarogentin from Swertia chirata, maesabalide III triterpenoide saponins from Maesa balansae, prenyloxy-naphthoquinone from Plubago zeylanica, plumbagin from Pera benensis and a list of 2-substituted quinaline alkaloids derived from Galipea longiflora.…”

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

“…108,162 A recent review clearly summarizes these results. 163 Disulfiram, a drug extensively used to treat alcoholism, has recently been reported to be active at nanomolar concentrations against the intracellular amastigotes of L. donovani. 164 Although clinical trials have not yet been carried out to assess the efficacy of disulfiram as monotherapy or in combination to treat different types of leishmaniasis, the implementation of a clinical trial is feasible, since disulfiram is a known and approved drug and, furthermore, is administered orally.…”