New synthetic aliphatic sulfonamido-quaternary ammonium salts as anticancer chemotherapeutic agents

• Published in: European journal of medicinal chemistry Vol. 69; pp. 670 - 677
• Main Authors: Song, Doona, Yang, Jee Sun, Oh, Changmok, Cui, Shuolin, Kim, Bo-Kyung, Won, Misun, Lee, Jang-ik, Kim, Hwan Mook, Han, Gyoonhee
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-11-2013
• Subjects: Aliphatic sulfonamido-quaternary ammonium salts; Anticancer chemotherapeutic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Molecular Structure; NSC126188; Open-ring moiety of quaternary ammonium salts; Perifosine; Quaternary Ammonium Compounds - chemical synthesis; Quaternary Ammonium Compounds - chemistry; Quaternary Ammonium Compounds - pharmacology; RhoB; rhoB GTP-Binding Protein - antagonists & inhibitors; rhoB GTP-Binding Protein - biosynthesis; rhoB GTP-Binding Protein - metabolism; Salts - chemical synthesis; Salts - chemistry; Salts - pharmacology; Structure-Activity Relationship; Sulfonamides - chemistry; Open-ring moiety of quaternary ammonium salts; Aliphatic sulfonamido-quaternary ammonium salts; Perifosine; NSC126188; Anticancer chemotherapeutic agents; RhoB
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.09.022

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.
[Display omitted] New aliphatic sulfonamido-quaternary ammonium salts were synthesized and evaluated for their activities. These results suggest that they are remarkably potent agents for anticancer chemotherapy through leading apoptosis.
•The novel 24 aliphatic sulfonamido-quaternary ammonium salts were synthesized.•18 compounds showed potent antitumor activities on gastric cancer cell lines.•Most of compounds induced up-regulation of the RhoB expression.•Compound 5b (propane-1,3-diamine derivative) induced the highest anticancer activity.