Synthesis and Evaluation of Thiochroman-4-One Derivatives as Potential Leishmanicidal Agents

ABSTARCT: The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand out as having promising biological activities due to their structural relationship with chromones (benzopyrans), which are widely known as privileged scaffolds in medicinal chemistry. In this work, we report the synthesis of 35 thiochromone derivatives and the in vitro antileishmanial and cytotoxic activities. Compounds were tested against intracellular amastigotes of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Compounds bearing a vinyl sulfone moiety, 4h, 4i, 4j, 4k, 4l and 4m, displayed the highest antileishmanial activity, with EC50 values lower than 10 μM and an index of selectivity over 100 for compounds 4j and 4l. When the double bond or the sulfone moiety was removed, the activity decreased. Our results show that thiochromones bearing a vinyl sulfone moiety are endowed with high antileishmanial activity and low cytotoxicity

Estructura y actividad de sapogeninas triterpenicas

La leishmaniasis es una enfermedad ampliamente difundida en América latina, desafortunadamente para su tratamiento hay muy pocas drogas, que tambien tienen una baja efectividad. Por esta razón el mundo urge de nuevas y más efectivas moléculas. En la búsqueda de sustancias antiparasitarias se detecto una alta actividad leishmanicida de Sapindus saponaria ricas en sapogeninas. El fraccionamiento y posterior purificación se obtuvieron tres sapogeninas triterpenicas cuyas estructuras se describen ene este articulo

SN 2023ixf in Messier 101: Photo-ionization of Dense, Close-in Circumstellar Material in a Nearby Type II Supernova

We present UV/optical observations and models of supernova (SN) 2023ixf, a type II SN located in Messier 101 at 6.9 Mpc. Early-time ("flash") spectroscopy of SN 2023ixf, obtained primarily at Lick Observatory, reveals emission lines of H I, He I/II, C IV, and N III/IV/V with a narrow core and broad, symmetric wings arising from the photo-ionization of dense, close-in circumstellar material (CSM) located around the progenitor star prior to shock breakout. These electron-scattering broadened line profiles persist for $\sim$8 days with respect to first light, at which time Doppler broadened features from the fastest SN ejecta form, suggesting a reduction in CSM density at $r \gtrsim 10^{15}$ cm. The early-time light curve of SN2023ixf shows peak absolute magnitudes (e.g., $M_{u} = -18.6$ mag, $M_{g} = -18.4$ mag) that are $\gtrsim 2$ mag brighter than typical type II supernovae, this photometric boost also being consistent with the shock power supplied from CSM interaction. Comparison of SN 2023ixf to a grid of light curve and multi-epoch spectral models from the non-LTE radiative transfer code CMFGEN and the radiation-hydrodynamics code HERACLES suggests dense, solar-metallicity, CSM confined to $r = (0.5-1) \times 10^{15}$ cm and a progenitor mass-loss rate of $\dot{M} = 10^{-2}$ M$_{\odot}$yr$^{-1}$. For the assumed progenitor wind velocity of $v_w = 50$ km s$^{-1}$, this corresponds to enhanced mass-loss (i.e., ``super-wind'' phase) during the last $\sim$3-6 years before explosion.Comment: 18 pages, 8 figures. Submitted to ApJ

Effect of substituents in the A and B rings of chalcones on antiparasite activity

10 p.-2 fig.- 2 tab.-1 schemChalcones are a group of natural products with many recognized biological activities, including antiparasitic activity. Although a lot of chalcones have been synthetized and assayed against parasites, the number of structural features known to be involved in this biological property is small. Thus, in the present study, 21 chalcones were synthesized to determine the effect of substituents in the A and B rings on the activity against Leishmania braziliensis, Trypanosoma cruzi, and Plasmodium falciparum. The compounds were active against L. braziliensis in a structure‐dependent manner. Only one compound was very active against T. cruzi, but none of them had a significant antiplasmodial activity. The electron‐donating substituents in ring B and the hydrogen bonds at C‐2′ with carbonyl affect the antiparasitic activity.Financial support: Minciencias and Universidad de Antioquia grant 111571249860, contract 061‐2016.Peer reviewe