Direct halogenation of phenolic compounds present in the CH2Cl2 extract of the roots of Arrabidaea brachypoda was investigated to enhance chemodiversity. The approach is based on eco-friendly reactions using NaBr, NaI, and NaCl in aqueous media to generate multiple 'unnatural' halogenated natural products from crude extracts. The halogenation reactions, monitored by UHPLC-PDA-ELSD-MS, were optimized to generate mono-, di-or tri-halogenated derivatives. To isolate these compounds, the reactions were scaled-up and the halogenated analogues were isolated by semipreparative HPLC-UV and fully characterized by NMR and HR-MS data. All of the original 16 halogenated derivatives were evaluated for their antiparasitic activities against the parasites Leishmania amazonensis and Trypanosoma cruzi.
Compounds presenting selective antiparasitic activities against one or both parasites with IC50values comparable to the reference were identified.
3The neglected tropical diseases represent a group of illnesses related to poverty and poor sanitation, and are mainly present in tropical and subtropical countries. Around 20 illnesses, currently affecting a billion individuals, totalize 12% of the total health burden in the world. 1 Among these diseases, leishmaniasis and Chagas disease are vectors transmitted via protozoan infections. Both infections suffer currently from limited chemotherapy and therefore are highly associated with huge social burdens, as well as the rise of morbidity and mortality. Thus, both diseases have a significant economic impact on the economy in developing countries. 2 Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 6-7 million people and can lead to severe myocarditis and/or complications of the digestive tract. 3 Chagas disease was mainly confined to Latin America, but in the last decades, it has spread to other continents. 4 T. cruzi infection is curable if treatment with one of the two drugs available, nifurtimox and benznidazole, is initiated soon after infection. 5 However, these drugs are associated with severe toxicity and have low efficacy to cure patients with chronic Chagas disease. 6 Since none of the currently available anti-T. cruzi drugs are ideal, new treatments for Chagas disease are urgently needed.Leishmaniasis is a group of diseases caused by protozoan parasites belonging to the Leishmania genus and transmitted by the bite of the female sand fly vector. 7 The diseases are endemic in 98 countries. Around 58,000 cases of visceral leishmaniasis and 220,000 cases of the cutaneous disease are officially reported annually worldwide. 8 The first-line treatment is performed with the pentavalent antimonials. Although still used, this chemotherapy presents several limitations, such as serious side effects, including patient death, a prolonged course of treatment, and the emergence of drug resistance. Second-line treatments, such as amphotericin B, pentamidine, and miltefosine, are also prescribed depending on the clinical manifestation and endemic zone. However, th...
