Design, synthesis and biological evaluation of steroidal glycoconjugates as potential antiproliferative agents.

Design, synthesis and biological evaluation of steroidal glycoconjugates as potential antiproliferative agents. ChemMedChem. 2021 Jan 21;: Authors: Du Z, Li G, Ge H, Zhou X, Zhang J Abstract To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of the steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized via the neoglycosylation approach. All the structures of the products were elucidated through NMR analysis and the stereochemistry of C20-MeON-pregnenolone (compound 8/9 ) were confirmed by crystal X-ray diffraction experiment. Their cytotoxicity on five human cancer cell lines was evaluated by the Cell Counting Kit-8 assay and structure-activity relationships (SAR) were discussed. Compound 5k displayed the most potent antiproliferative activities against HepG2 cells with the IC 50 values of 1.5 µM. The further pharmacological experiments of compound 5k on HepG2 cells revealed that it could cause morphological changes and cell cycle arrest at G0/G1 phase and then induced the apoptosis which may be associated with the enhanced expression of High-mobility group Box 1 (HMGB1). Taken together, these findings provide that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents. PMID: 33476082 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research