2. Academic Validation
  3. Enzymatic biosynthesis and biological evaluation of novel 17-AAG glucoside as potential anti-cancer agents

Enzymatic biosynthesis and biological evaluation of novel 17-AAG glucoside as potential anti-cancer agents

  • Bioorg Med Chem Lett. 2020 Aug 1;30(15):127282. doi: 10.1016/j.bmcl.2020.127282.
Hong-Mei Li 1,  Bohan Li 1,  Xiaolong Sun 1,  Hui Ma 1,  Meilin Zhu 1,  Yiquan Dai 1,  Tao Ma 1,  Yu Li 2,  Young-Soo Hong 3,  Cheng-Zhu Wu 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, Anhui, China.
  • 2 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • 3 Anticancer Agent Research Center, KRIBB, Cheongju 28116, Republic of Korea.
  • 4 School of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, Anhui, China. Electronic address: wuchengzhu0611@bbmc.edu.
PMID: 32527461 DOI: 10.1016/j.bmcl.2020.127282
Abstract

A novel 17-allylamino-17-demethoxygeldanamycin (17-AAG) glucoside (1) was obtained from in vitro enzymatic glycosylation using a UDP-glycosyltransferase (YjiC). The water-solubility of compound 1 was approximately 10.5 times higher than that of the substrate, 17-AAG. Compound 1 showed potential anti-proliferative activities against five human Cancer cell lines, with IC50 values ranging from 5.26 to 28.52 μM. Further studies also indicated that compound 1 could inhibit the growth of CNE-2Z cells by inducing the degradation of HSP90 client proteins (Akt, c-Raf, Bcl-2, and HIF-1α). In addition, compound 1 showed greater potential anti-tumor efficacy than 17-AAG in nude mice xenografted with CNE-2Z cells. Therefore, we suggest that in vitro enzymatic glycosylation is a powerful approach for the structural optimization of 17-AAG.

Keywords

17-AAG; Anti-cancer; Glycosylation; Hsp90; Water-solubility.

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