Mesoionic Oxatriazoles (MOTA): NO-Donating Characteristics and Pharmacology

Abstract

Biological role of nitric oxide (NO), functioning of isoforms of NO synthetases (NOS) and pharmacology of principle NO-donors were reviewed. NO donating characteristics and pharmacology of 23 mesoionic oxatriazoles (MOTA) were compared with those of 5-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (NaNP) and glyceryl trinitrate (GTN). It is concluded that in vitro NO donating profile of MOTA hardly can be used as a predicting measure for their pharmacological activities either in vitro or in vivo. If anything, fast NO releasers seem to be stronger vasorelaxants than MOTA with slow NO releasing properties. Still, among representatives of this last category of MOTA one may find efficient antithrombotic and thrombolytic agents. For instance, MOTA 5-oxides were more potent thrombolytics than SIN-1, SNAP or NaNP. Also MOTA with potent anti-platelet action in vitro seem to be potent relaxants of tracheal strips. In summary, by manipulating the chemical structures of MOTA one may obtain relative selectivity towards vasorelaxant, anti-platelet, thrombolytic or tracheorelaxant properties. Thus different categories of MOTA might be designed with a hope of achieving hypotensive, antithrombotic, thrombolytic or anti-asthmatic drugs.

The Chemistry of Bioactive Mesoionic Heterocycles

“…The biological activity was reported by Masuda et al in 1971 [56]. Oxatriazole-5-imines (9) have been reported to be an important class of NO donors and potent antiplatelet, fibrinolytic, thrombolytic, and bronchiectatic agents [57]. However, an extensive investigation of the NO-releasing and other biologi-cal properties of the mesoionic oxatriazole derivatives has been started by researchers at the GEA Farmaceutisk Fabrik, Copenhagen, who synthesized a large number of this class of compounds.…”

“…3-Aryl-4-formylsydnones (22) are attractive starting compounds for several 4-heterocycle-substituted sydnones, such as thiazolidinone (23) and thiazoline (24,25) [14,15], imidazoles (26) [16], thiadiazolines (27), thiadiazoles (28) [17], and indoles (29) [18]. Some sydnonylsubstituted thiazolidinone (23) and thiazoline (30) derivatives exhibited a potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, comparable to that of vitamin E [14,15].…”

“…There are a number of reviews published in the field of NO donors [24][25][26][27][28]. This review will therefore focus on recent advances in NO-donor mesoionic compounds, sydnonimines (3), and 1,2,3,4-oxatriazolium-5-aminides (9), which have drawn the most interest today [26,29].…”

“…For instance, MOTA 5-oxides were more potent thrombolytics than SIN-1, SNAP, or NaNP. By manipulating the chemical structures of MOTA, hypotensive, antithrombotic, thrombolytic, or antiasthmatic drugs might be designed [65].…”

Antileishmanial Activity of 1,3,4-Thiadiazolium-2-Aminide in Mice Infected withLeishmania amazonensis

“…These characteristics have been revealed by interesting biological activities including anti-inflammatory, analgesic, antibacterial, antifungal, and antitumor activities (22). In addition, this class of mesoionic compounds is known to have nitric oxide (NO)-releasing properties (11).…”