SAR study on thiolato-bridged triosmium carbonyl clusters: higher reactivity does not equal higher antiproliferative activity

• Main Authors: Liang, Xin, Leong, Weng Kee
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2025
• Subjects: Chemistry; Antiproliferative activity; Antineoplastic Agents
• Online Access: https://hdl.handle.net/10356/182219
• Institution: Nanyang Technological University

A structure-activity relationship study on triosmium clusters of the general formula Os3(μ-H)(μ-SC6H4X)(CO)10 (2-X, where X = o-, m- or p-NH2; o-, m- or p- OH; p-H, -Br, -NO2, -COOH or -CH2COOH) show that their antiproliferative activity is through the cluster core, and the nature and position of the phenyl ring substituent X shows a significant impact on the activity. Clusters with an electron-withdrawing group are more reactive but are thus quickly consumed through reaction with serum, while those with an electron-donating group persists sufficiently to enter the cells and result in higher antiproliferative activity. Interestingly, m-substituted clusters and those with lipophilicity >6.0 also exhibit higher antiproliferative activity. In contrast, o-substituted clusters capable of intramolecular hydrogen bonding have lower cytotoxicity. The cluster 2-m-OH, with higher antiproliferative activity and lower reactivity with serum, is a potential lead compound for further mode of action studies.