Abstract: A series of biheterocyclic assemblies comprising of 1,2,5-oxadiazole and azasydnone scaffolds were synthesized and biologically evaluated as novel nitric oxide (NO)-donor and antiplatelet agents. Depending on functional substituents at the biheterocyclic core, all studied compounds demonstrated good NO-donor profiles releasing NO in a wide range of concentrations (19.2%–195.1%) according to a Griess assay. (1,2,5-Oxadiazolyl)azasydnones showed excellent antiplatelet activity in the case of ADP and adrenaline used as inducers completely suppressing the aggregate formation even at the lowest test concentration of 0.0375 μmol/ml, which is a rather unique feature. Moreover, studied biheterocycles possess a selective mechanism of inhibition of platelet aggregation mediated only by ADP and adrenaline, which are considered to be the main inducers causing thrombus formation. In addition, (1,2,5-oxadiazolyl)azasydnones were found to be completely non-toxic to hybrid endothelial cells EaHy 926. Studies of hydrolytic degradation of the synthesized compounds afforded benzoic acid as a sole detectable decomposition product, which is considered advantageous in drug design. Therefore, (1,2,5-oxadiazolyl)azasydnones represent a novel class of promising drug candidates with improved antiplatelet profile and reduced toxicity enabling their huge potential in medicinal chemistry and drug design.

Cite: Zhilin E.S. , Ustyuzhanina N.E. , Fershtat L.L. , Nifantiev N.E. , Makhova N.N.
Antiaggregant effects of (1,2,5‐oxadiazolyl)azasydnone ring assemblies as novel antiplatelet agents
Chemical Biology & Drug Design. 2021. V.100. N6. P.1017-1024. DOI: 10.1111/cbdd.13918 WOS Scopus OpenAlex

Identifiers:

Web of science:	WOS:000674140600001
Scopus:	2-s2.0-85110426137
OpenAlex:	W3177903186

Citing:

DB	Citing
OpenAlex	18
Scopus	16
Web of science	17

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