Design, Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents. (19th February 2021)

• Record Type: Journal Article
• Authors: Du, Zhichao; Li, Guolong; Ge, Haixia; Zhou, Xiaoyang; Zhang, Jian
• Is Part Of: ChemMedChem. Volume 16:Number 9(2021)
• Page Start: 1488
• Page End: 1498
• Publication Date: 2021-02-19
• Subjects: anticancer -- glycosides -- high-mobility group box 1 -- neoglycosylation -- steroids; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000966
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20‐MeON‐pregnenolone was confirmed by crystal X‐ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit‐8 assay, and structure–activity relationships (SAR) are discussed. 2‐deoxy‐d ‐glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC50 value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell‐cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high‐mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents. Abstract : Four series of steroidal MeON‐neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized by the neoglycosylation approach. The most potential compound with an IC50 value of 1.5 μM on HepG2 cells could cause cell‐cycle arrest at the G0/G1 phase and induce apoptosis.