Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

<p>The natural product lupeol <b>1</b> was isolated from aerial parts of <i>Vernonia scorpioides</i> with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives <b>2–11</b> were prepared by classical procedures. Including, five new esters derivatives <b>7–11,</b> which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol <b>1–11</b> were confirmed by ¹H NMR, ¹³C NMR and HRMS. Their antiprotozoal activity was evaluated <i>in vitro</i> against <i>L. amazonensis</i> and <i>T. cruzi.</i> Derivative <b>6</b> showed the best antitrypanosomal activity (IC₅₀ = 12.48 μg/mL) and the lowest cytotoxic derivative (CC₅₀ = 161.50 μg/mL). The mechanism of action of the most active derivatives (<b>4, 6</b> and <b>11</b>) is not dependent from the enzyme trypanothione reductase.</p

Composite Hydrogels with Tunable Anisotropic Morphologies and Mechanical Properties

Fabrication of anisotropic hydrogels exhibiting direction-dependent structure and properties has attracted great interest in biomimicking, tissue engineering, and bioseparation. Herein, we report a freeze-casting-based fabrication of structurally and mechanically anisotropic aerogels and hydrogels composed of hydrazone cross-linked poly­(oligoethylene glycol methacrylate) (POEGMA) and cellulose nanocrystals (CNCs). We show that, by controlling the composition of the CNC/POEGMA dispersion and the freeze-casting temperature, aerogels with fibrillar, columnar, or lamellar morphologies can be produced. Small-angle X-ray scattering experiments show that the anisotropy of the structure originates from the alignment of the mesostructures, rather than the CNC building blocks. The composite hydrogels show high structural and mechanical integrity and a strong variation in Young’s moduli in orthogonal directions. The controllable morphology and hydrogel anisotropy, coupled with hydrazone cross-linking and biocompatibility of CNCs and POEGMA, provide a versatile platform for the preparation of anisotropic hydrogels