Enantioselectivity in endocrine disrupting effects of four cypermethrin enantiomers based on in vitro models.

Cypermethrin (CP) is a kind of chiral pesticides that has been defined as endocrine disrupting chemical. The diversity in bioactivity, toxicity, metabolism, bioaccumulation, and degradation behaviors of CP enantiomers as well as the research deficiency had made the risk assessment of CP enantiomers very complicated. Herein, four CP enantiomers were separated as target chemicals to investigate their enantioselective endocrine disrupting effects. Firstly, dual-luciferase reporter gene assays were adopted to investigate their potential endocrine disrupting effects via various receptors. The expression levels of steroid hormones related genes and hormone secretion levels in H295R cell were measured to verify the results. Results from the reporter gene assay showed that 1R-cis-αS-CP (CP11) exhibited glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and thyroid receptor (TR) antagonistic activity with the RIC20 values of 9.22 × 10-7, 3.33 × 10-7, and 4.47 × 10-7 M, respectively; 1R-trans-αS-CP (CP21) also showed androgen receptor (AR) agonist activity and estrogen receptor (ER) antagonistic activity with the REC20 and RIC20 values were 1.07 × 10-4 M and 4.78 × 10-6 M, respectively. Results of qRT-PCR and hormone measurement also showed that CP11 and CP21 could disturb the expression of steroid hormones related genes and hormone secretion accordingly. Results provided here can help to understand the enantioselective ecological and health risks of CP enantiomers comprehensively and provide constructive guidance for the safe use of chiral pesticides and the invention of green pesticides.

Lenalidomide, a blockbuster drug for the treatment of multiple myeloma: Semipreparative separation through supercritical fluid chromatography and vibrational circular dichroism spectroscopy.

Semipreparative separation of lenalidomide has been performed through supercritical fluid chromatography. In regard to retention and resolution of lenalidomide, effects of chromatographic conditions, such as chiral stationary phases, organic co-solvents, mobile phases, and column temperature, have been studied in detail. Amylose tris(3, 5-dimethylphenylcarbamate)-coated and the single-urea-bound ß-cyclodextrin chiral stationary phases exhibited good separation performances for lenalidomide in the CO2 /methanol mixture. Then, a comparative study of semipreparative separation of lenalidomide has been carried out on these two chiral stationary phases. As indicated, separation of lenalidomide on the ß-cyclodextrin-bound column was much better than the other. Under the optimized conditions, the loading per injection was 30 mg, the cycle time was 5 min, and the recoveries of two enantiomers were about 81.7 and 79.5%, respectively. Moreover, the vibrational circular dichroism spectrum of the first-eluted enantiomer in d6 -dimethylsulfoxide solution was consistent with the calculated pattern based on the S configuration, revealing that it should be (S)-(-)-lenalidomide. Briefly, this separation method through supercritical fluid chromatography might provide favorable information for rapid separation, enantioselective assessment, and absolute configurations of chiral pharmaceuticals.