Abstract
RhoB is expressed during tumor cell proliferation, survival, invasion, and metastasis. In malignant progression, the expression levels of RhoB are commonly attenuated. RhoB is known to be linked to the regulation of the PI3K/Akt survival pathways. Based on aliphatic amido-quaternary ammonium salts that induce apoptosis via up-regulation of RhoB, we synthesized novel aliphatic sulfonamido-quaternary ammonium salts. These new synthetic compounds were evaluated for their biological activities using an in vitro RhoB promoter assay in HeLa cells, and in a growth inhibition assay using human cancer cell lines including PC-3, NUGC-3, MDA-MB-231, ACHN, HCT-15, and NCI-H23. Compound 5b (ethyl-dimethyl-{3-[methyl-(tetradecane-1-sulfonyl)-amino]-propyl}-ammonium; iodide) was the most promising anticancer agent in the series, based upon the potency of growth inhibition and RhoB promotion. These new aliphatic sulfonamido-quaternary ammonium salts could be a valuable series for development of new anticancer chemotherapeutic agents.
| Original language | English |
|---|---|
| Pages (from-to) | 670-677 |
| Number of pages | 8 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 69 |
| DOIs | |
| Publication status | Published - 2013 |
Bibliographical note
Funding Information:This research was supported by a grant from the National Research Foundation (grant 2012-0000884 ), the Translational Research Center for Protein Function Control ( NRF-2009-0083522 ), the Basic Science Research Program ( NRF-2013R1A1A2008165 ), the Korea Health21 R&D Project, Ministry of Health & Welfare ( A120478 ), and the Brain Korea 21 Program, Republic of Korea .
All Science Journal Classification (ASJC) codes
- Pharmacology
- Drug Discovery
- Organic Chemistry
