20261-39-6Relevant academic research and scientific papers
Differential lethal action of C17:2 and C17:0 anacardic acid derivatives in Trypanosoma cruzi – A mechanistic study
Costa Silva, Thais A.,Guadagnin, Rafael C.,Mendes, Viviane M.,Sartorelli, Patricia,Tempone, Andre G.,Umehara, Eric,Lago, Jo?o Henrique G.
, (2020)
The n-hexane extract from leaves of Schinus terebinthifolius (Anacardiaceae) induced 100% of death of trypomastigote forms of T. cruzi at 300 μg/mL and was subjected to a bioactivity-guided fractionation to afford a C17:2 derivative of anacardic acid [6-(8′Z,11′Z)-heptadecadienyl-salicylic acid, 1]. Additionally, compound 1 was subjected to hydrogenation procedures to afford a C17:0 derivative (6-heptadecanyl-salicylic acid, 1a). Compounds 1 and 1a were effective in killing trypomastigote forms of T. cruzi with IC50 values of 8.3 and 9.0 μM, respectively, while a related compound, salicylic acid, was inactive. Furthermore, no cytotoxicity was observed for the highest tested concentration (CC50 > 200 μM) for all evaluated compounds. Due to the promising results, the mechanism of parasite death was investigated for compounds 1 and 1a using flow cytometry and spectrofluorimetry. The cell membrane permeability assay with SYTOX Green indicated that compound 1 significantly altered this parameter after 40 min of incubation, while compound 1a caused no alteration. Considering that the hydrogenation rendered a differential cellular target in parasites, additional assays were performed with 1a. Despite no permeabilization of the plasma membrane, compound 1a induced depolarization of the electric potential after two hours of incubation. The mitochondria of the parasite were also affected by compound 1a, with depolarization of the mitochondrial membrane potential, and reduction of reactive oxygen species (ROS) levels. The Ca2+ levels were not affected during the time of incubation. Considering that the mitochondrion is a single organelle in Trypanosoma cruzi for ATP generation, compounds affecting the bioenergetic system are of interest for drug discovery against Trypanosomatids.
Synthesis of Anacardic Acids
Zehnter, Reinhard,Gerlach, Hans
, p. 2209 - 2220 (2007/10/03)
The anacardic acids 1-11, isolated from various plants, were synthesized by a new general method.Reaction of the methyl alkynoates 12-18 with 1-methoxy-1,4-cyclohexadiene at 200 deg C afforded directly the methyl 2-methoxybenzoates 19-25 with long chain substituents in 6-position in 74-85percent yield.The dienophiles 12-16 were prepared by pyrolysis of the corresponding acylphosphoranes 26-30, the dienophiles 17 and 18 by methoxycarbonylation of the corresponding alkynes 31 and 32 via the hydroxy esters 33 and 34.Demethylation of 19-23 with AlI3 gave the methyl salicylates 35-39 which could be hydrolized to the anacardic acids 1-4 and 7.Hydrolysis of 24 and 25 provided the hydroxy acids 40 and 41, which were converted by treatment with CBr4/PPh3 into the acids 42 and 43 bearing bromoalkyl side chains.These were transformed into 44-47 by reaction with 1-hexynyllithium and 1-octynyllithium.Stereoselective hydrogenation of 44-47 gave 48-51 with (Z)-alkene side chains.In a similar approach 42 was converted into 52 and then into 53, which gave upon treatment with 1-pentynylmagnesium bromide or 1-heptynylmagnesium bromide the acids 54 and 55 with alkadiyne side chains.Stereoselective hydrogenation provided 56 and 57 with (Z,Z)-alkadiene side chains.The 2-methoxy group in 48-51, 56, 57 was demethylated by treatment with AlI3 to give the anacardic acids 5, 6, 8-11. - Keywords: Anacardic acids; Benzoates, methyl 6-alkyl-2-methoxy-; 2-Alkynoates, methyl; Aluminium triiodide, demethylation by treatment with
