A New Pyridopyrimidine Derivative May Treat Diarrhea

Compound may work against diarrhea, a major cause of childhood death in developing countries

THURSDAY, June 19 (HealthDay News) -- A newly identified pyridopyrimidine derivative that works against a toxin released by powerful strains of Escherichia coli may be effective against diarrhea, according to study findings published in the June 17 issue of the Proceedings of the National Academy of Sciences.

Alexander Y. Kots, Ph.D., of the University of Texas Health Science Center in Houston, and colleagues screened a compound library in order to identify a class of pyridopyrimidine derivatives that can suppress STa-dependent cGMP accumulation in cultured human colorectal carcinoma.

The investigators found that the compound, known as BPIPP, achieved a significant reduction in accumulation of cyclic nucleotides (molecules that stimulate secretion of salt and water, causing diarrhea). While the exact effects remain unknown, the researchers suggest BPIPP slows production of cyclic nucleotides by toxin-stimulated intestinal cells.

"BPIPP is a promising lead compound that suppresses stimulated synthesis of cyclic nucleotides, cAMP and cGMP, in intact cells," the authors conclude, but they cautioned that more work is needed before it is ready for clinical trials. "BPIPP can be used for localized tissue treatment of disorders with excessive production of cyclic nucleotides without undesirable, systemic effects."

Abstract
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