Identification of nitric oxide donors by biomimetic HTS application.
Metalloporphyrin catalyzed biomimetic oxidation was used for the identification of nitric oxide (NO) donors with diverse chemical structure. Methodology was validated by testing known NO donors. Efficient automation of the test allowed us to investigate a subset of our corporate library. Several hits identified in this campaign were validated in both the chemical and also microsomal model that revealed all hits to be active in the biological system, as well. One of the hits showed comparable activity to V-PYRRO/NO, the prototypic liver selective NO donor.
Balogh
György T
GT
Pilot Plant II, Gedeon Richter Ltd., P.O. Box 27, H-1475, Budapest, Hungary.
Dalmadi
Balázs
B
Bielik
Attila
A
Keserü
György M
GM
D000818:Animals; D032701:Biomimetics; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008862:Microsomes, Liver; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D008665:Metalloporphyrins; D020030:Nitric Oxide Donors; D006861:Hydrogen Peroxide