Triaminopyrimidine derivatives as transmembrane HCl transporters.

Abstract

Small synthetic molecules capable of inducing transmembrane anion transport have received a lot of attention as potential anti-cancer agents due to their ability to interfere with intracellular pH homeostasis. A series of triaminopyrimidine-based anion transporters have been synthesised, and they are found to diminish proton gradients across lipid bilayers at physiologically relevant pH. The compounds have pKa values (≈7.2) that allow protonation/deprotonation processes coupled with anion binding/unbinding events in physiologically relevant conditions. Synthetic vesicle transport experiments as well as solid state structures indicate synergistic binding of HCl. Cell assays show that the transporters induce apoptosis in various cancerous cell lines.

• Authors: Petr Motloch, Ana Guerreiro, Carolina Q Azeredo, Gonçalo J L Bernardes, Christopher A Hunter, Istvan Kocsis
• Journal: Organic & biomolecular chemistry (Org Biomol Chem) Vol. 17 Issue 22 Pg. 5633-5638 (06 05 2019) ISSN: 1477-0539 [Electronic] England
• PMID: 31120093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pyrimidines
• pyrimidine
• Hydrochloric Acid

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Biological Transport (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• HEK293 Cells
• Humans
• Hydrochloric Acid (chemistry, metabolism)
• Ion Transport (drug effects)
• Molecular Structure
• Pyrimidines (chemical synthesis, chemistry, pharmacology)