T1 Laurequinone, a lead compound against Leishmania A1 López Arencibia, Atteneri A1 García-Davis, Sara A1 López-Arencibia, Atteneri A1 Bethencourt-Estrella, Carlos J. A1 San Nicolás-Hernández, Desirée A1 Viveros-Valdez, Ezequiel A1 Díaz-Marrero, Ana R. A1 Fernández, José J. A1 Piñero, José E. A1 Lorenzo Morales, Jacob K1 laurequinone K1 sesquiterpene K1 Laurencia K1 Leishmania amazonensis K1 leishmaniasis AB Among neglected tropical diseases, leishmaniasis is one of the leading causes, not onlyof deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites ofthe genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, andvisceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for thepatient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii havebeen studied for this purpose. The different compounds were tested in vitro against the promastigoteand amastigote forms of Leishmania amazonensis. Different assays were also performed, includingthe measurement of mitochondrial potential, determination of ROS accumulation, and chromatincondensation, among others, focused on the detection of the cell death process known in this type oforganism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity:laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 valuesagainst promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was themost potent compound tested and was shown to be more effective than the reference drug miltefosineagainst promastigotes. Different death mechanism studies carried out showed that laurequinoneappears to induce programmed cell death or apoptosis in the parasite studied. The obtained resultsunderline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent SN 1660-3397 YR 2023 FD 2023 LK http://riull.ull.es/xmlui/handle/915/35827 UL http://riull.ull.es/xmlui/handle/915/35827 LA en DS Repositorio institucional de la Universidad de La Laguna RD 24-nov-2024