Development of Chemical Probes for Functional Analysis of Anticancer Saponin OSW‐1

Abstract

Chemical probe‐based approaches have proven powerful in recent years in the target identification studies of natural products. OSW‐1 is a saponin class of natural products with highly potent and selective cytotoxicity against various cancer cell lines. Understanding its mechanism of action is important for the development of anticancer drugs with potentially novel target pathways. This account reviews recent progress in the development of OSW‐1 derived probes for exploring the mechanism of its action. The key to the probe development is a judicious choice of functionalization sites and a selective functionalization strategy. The types of probes include fluorescent probes for cellular imaging analysis and affinity probes for target identification analysis.

Natural-product-based fluorescent probes: recent advances and applications

“…11a), a natural saponin isolated from the bulbs of Ornithogalum saundersiae , has antiviral and anticancer activities with a novel mechanism of action. 42 The structure of 38 contains a partially acylated disaccharide moiety attached at the D-ring of steroidal aglycone. Compound 38 exhibits a remarkably potent anticancer activity (average GI 50 = 0.78 nM for in vitro NCI-60 cell line screening) with 10–100-fold selectivity for cancer cell lines over nonmalignant cells.…”

“…11a), a natural saponin isolated from the bulbs of Ornithogalum saundersiae, has antiviral and anticancer activities with a novel mechanism of action. 42 The structure of 38 contains a partially acylated disaccharide moiety attached at the D-ring of steroidal aglycone.…”

Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review

“…Nowadays, chemical probe-based approaches have emerged as powerful methods for mechanistic studies of natural products by identifying the cellular site of action, the target proteins, and the target cellular pathways. However, studies on the development of chemical probes of OSW-1 for investigation of its biological role are still lacking ( 30 ). Recently, network pharmacology approaches for predicting unexplored targets and therapeutic potential are being applied increasingly to find new therapeutic opportunities of natural products ( 102 ).…”

“…However, none of these studies have further explored the specific action targets of each functional group. In recent years, chemical probe-based approaches were proven powerful in the target identification studies of natural products ( 30 ). This may become a strong tool for studying the action targets of OSW-1 in the future.…”

Synthesis and Antiproliferative Activities of OSW‐1 Analogues Bearing 2”‐O‐p‐Acylaminobenzoyl Residues†

“…[ 28‐34,36‐41 ] It is of great interest to identify the antitumor‐associated binding proteins, which could be exploited as drug targets for cancer treatment. Recently, Sakurai and co‐workers synthesized several OSW‐1‐based probes with fluorescent tags installed at C3” or C4” on the xylose residue, [ 42‐47 ] and found these probes could localize to the ER and Golgi apparatus in HeLa cells and induce Golgi stress. [ 41 ]…”