Chroman-4-one hydrazones derivatives: synthesis, characterization, and in vitro and in vivo antileishmanial effects

Synthesis and Evaluation of Antileishmanial and Cytotoxic Activity of Benzothiopyrane Derivatives

“…The previous esters and amides were prepared thinking of performing a SAR study to analyze the effect of chain size on leishmanicidal and cytotoxic activity, but all these compounds showed very low activity. Surprisingly, two acyl hydrazones 26a and 26b showed a marginal activity EC 50 28.5 and 53.2 µM, unlike the compounds that we have previously analyzed [8], which seems to indicate that the substitution by a C-2 carbonyl of a thiochroman-4-one interferes with its mechanism of action against amastigotes of L. panamensis parasites.…”

“…However, this task is a priority for the pharmaceutical industry, so the affected countries must seek their own alternatives. Recently we reported the in vivo leishmanicidal activities of compounds bearing a benzothiopyran scaffold and also the acyl hydrazones derived from chroman and thiochromans [8,23]. To optimize their effects, in this work we prepared thirty-two compounds, including thiochromenes, thichroman-4-ones and acyl hydrazones substituted in C-2 or C-3 with carbonyl/nitrile or carboxyl groups.…”

“…From a bioisosteric point of view, replacement of the oxygen atom (O) by a sulfur atom (S) it may cause significant changes in the pharmacology activity since the changes in electron-donating potential and the size of sulfur cause solubility [6], polarity, hydrogen bonding and metabolism [7] modifications. In a previous paper, we have reported that acyl hydrazone derivatives of chromanone and thiochromanone have good in vivo antileishmanial activity with effective concentration (EC 50 ) values of 20.1 and 25.0 µM respectively, in addition to anti-inflammatory and wound-healing properties [8]. Besides, acyl hydrazone derivatives of thiochroman-4-ones have been reported as potent inhibitors of cysteine proteases which has implications in the treatment of Chagas' disease [9,10].…”

Nanoemulsions for increased penetrability and sustained release of leishmanicidal compounds

“…The percentage of positive events for green fluorescence and the number of parasites inside the infected cells were quantified according to the mean fluorescence intensity (MFI) using histograms. [ 9,11 ] Infected but nonexposed cells kept under the same conditions were used to control infection, while infected cells exposed to AMB were tested as leishmanicidal control. The tests were conducted at least twice, with three replicates per concentration evaluated.…”

“…[ 9 ] Furthermore, TC1 and TC2 [ 10 ] compounds derived from chromon and thiochromon compounds, formulated as a 4% ointment, showed an excellent therapeutic response when administered topically in hamsters with CL caused by L. braziliensis . [ 11 ] Both compounds affect the processes associated with the functioning of parasite mitochondria, induce oxidative stress, and inhibit protease activity in L. braziliensis . [ 12 ] Moreover, a curative effect was recently reported in dogs with CL after treatment with an ointment containing 2% TC2 and 2% a mixture of triterpene saponins.…”