Molecular Dynamics of Steroidal Rotors Probed by Theoretical, Spectroscopic and Dielectric Methods.

Our study focuses on molecular rotors with fast-moving rotators and their potential applications in the development of new amphidynamic crystals. Steroidal molecular rotors with a dipolar fluorine-substituted phenyl group as the rotator were synthesized and characterized. Three different rotors were investigated with varying numbers of fluorine atoms. A comprehensive analysis was performed using vibrational spectroscopy (Raman, FT-IR), electronic circular dichroism (ECD), and dielectric response to understand the behavior of the investigated model rotors. The results were supported by theoretical calculations using Density Functional Theory (DFT) methods. The angle-dependent polarized Raman spectra confirmed the crystallinity of the samples. Nearly frequency and temperature-independent permittivity suggest low-frequency librational motion of stators. An in-depth analysis of ECD spectra revealed high conformational flexibility in solution, resulting in low ECD effects, while in the solid-state with restricted rotation, significant ECD effects were observed. These findings shed light on the conformational behavior and potential applications of the studied steroidal molecular rotors.

In vitro, ex vivo and in vivo short-term screening of DHEA nitrate derivatives activity over Trypanosoma cruzi Ninoa and TH strains from Oaxaca State, México.

Chagas disease is a health problem that affects millions of persons, currently Nifurtimox (Nfx) and Benznidazole (Bz) are the unique drugs to treat it. However, these drugs produce adverse effects and high toxicity, which has motivated the search for new candidate drugs. Based on reports about the extensive biological activity of steroidal nitrate esters, in this study three nitrate esters steroids (1b, 2b and 4b) were synthetized and characterized from Dehydroepiandrosterone (DHEA, 1a), 19-hydroxy-DHEA (2a), and Androst-5-en-3ß,17ß-diol (4a), respectively. In addition, compounds 3a and 3b were obtained by introducing an α-ethynyl and a ß-hydroxyl groups at position 17 of 2b and further nitration of the hydroxyl group. The trypanocidal activity of these steroids was evaluated in vitro against the epimastigote stage of two T. cruzi strains, Ninoa and TH, and their cytotoxicity over J774.2 macrophage cell line was assayed. Compounds 3a, 3b, and 4a shown higher trypanocidal activity than Bz and Nfx against epimastigotes of Ninoa strain, whereas DHEA (1a) and its nitrate derivative 1b showed higher activity than the reference drugs against the TH strain epimastigote. None of the compounds showed activity in the ex vivo assays against the blood trypomastigote of both strains. Interestingly, the selectivity index of Androst-5-en-3ß,17ß-diol 4a was almost twice the value of Nfx and 50 times more than Bz, against Ninoa and TH strains, respectively. Therefore, compound 4a could represent a valuable starting point toward the optimization of steroid derivatives as trypanocidal agents.