IN VITRO LEISHMANICIDE ACTIVITY OF SYNTHETIC DERIVATIVES OF PURPUROGALIN
Leishmaniasis. Purpurogaline derivatives. Neglected diseases
Leishmaniasis is an infectious, non-contagious disease that has protozoa of the genus Leishmania as its etiological agent . A disease with a broad clinical spectrum, considered a public health problem in many countries, with poor treatments mainly due to toxicity, variable efficacy and the ability to induce parasitic resistance. Knowing that the existing pharmacotherapy is unsatisfactory, it is essential to plan and develop new drugs, one of the main strategies for this is the discovery of new drug prototypes through chemical synthesis. Thus, the aim of the present study was to investigate the in vitro cytotoxic and leishmanicidal activity of purpurogaline derivatives aiming at the discovery of new prototype candidates for leishmanicidal drugs . Through the colorimetric assay of MTT and the leishmanicidal activity in cultures of L. chagasi and L. amazonensis promastigotes through direct counting under an optical microscope. Statistical analyzes were performed using the GraphPad Prism software . The derivatives tested showed cytotoxicity below 60% to the host cell up to the maximum tested concentration of 100 µM, with the exception of derivatives IAS 2 and IAS 5. In the evaluation of direct activity on L. chagasi promastigotes, derivatives IAS 6 to IAS 8 showed maximum effect (ME) greater than 98% and IC50less than 20 µM, with an MS of 99.27 ± 1.46 %, 98.10 ± 3.30 % and IC50 of 10.08 µM (5.11 - 18.46), 9.46 µM (6 .08 – 14.23), respectively. Against L. amazonenses, derivatives IAS 3, IAS 4, IAS 5 and IAS 7 presented IC50 below 30 µM and MS above 60%, with emphasis on IAS 3 with IC50 of 17.97 (7.76 – 41.99 ) and MS of 100%. The derivatives have shown promise molecules for their activity leishmanicide, however , aspects related to the toxicity of some derivatives also p fear be improved.