Chemical structure of retro-2, a compound that protects cells against ribosome-inactivating proteins

Jewn Giew Park, Jennifer Nielsen Kahn, Nilgun E. Tumer, Yuan Ping Pang

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Shiga-like toxins and ricin are ribosome-inactivating proteins (RIPs) that are lethal to mammals and pose a global health threat. No clinical vaccines or therapeutics currently exist to protect against these RIPs. Two small molecules (Retro-1 and Retro-2) were discovered with high-throughput screening and reported for their protection of cells against RIPs. Of great significance, Retro-2, reported as (E)-2-(((5-methylthiophen-2-yl)methylene)amino)-N- phenylbenzamide, fully protected mice from lethal nasal challenge with ricin. Herein, we report studies showing that the chemical structure of Retro-2 is (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3-dihydroquinazolin-4(1H)-one rather than (E)-2-(((5-methylthiophen-2-yl)methylene)amino)-N-phenylbenzamide. The latter is an achiral molecule that converts spontaneously to the former, which is a racemate and showed cell protection against RIPs. This calls for attention to (±)-2-(5-methylthiophen-2-yl)-3-phenyl-2,3- dihydroquinazolin-4(1H)-one as a promising RIP inhibitor and for chemical characterization of drug leads obtained from high-throughput screens.

Original languageEnglish (US)
Article number631
JournalScientific reports
Volume2
DOIs
StatePublished - 2012

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