MyJournals Home  

RSS FeedsIJMS, Vol. 23, Pages 14942: 1,2,3-Triazole Derivatives as Novel Antifibrinolytic Drugs (International Journal of Molecular Sciences)

 
 

29 november 2022 10:55:36

 
IJMS, Vol. 23, Pages 14942: 1,2,3-Triazole Derivatives as Novel Antifibrinolytic Drugs (International Journal of Molecular Sciences)
 


Fibrinolysis is a natural process that ensures blood fluidity through the removal of fibrin deposits. However, excessive fibrinolytic activity can lead to complications in different circumstances, such as general surgery or severe trauma. The current antifibrinolytic drugs in the market, aminocaproic acid (EACA) and tranexamic acid (TXA), require high doses repetitively to maintain their therapeutic effect. These high doses are related to a number of side effects such as headaches, nasal symptoms, or gastrointestinal discomfort and severely limit their use in patients with renal impairment. Therefore, the discovery of novel antifibrinolytics with a higher specificity and lower dosage could vastly improve the applicability of these drugs. Herein, we synthesized a total of ten compounds consisting of a combination of three key moieties: an oxadiazolone, a triazole, and a terminal amine. The IC50 of each compound was calculated in our clot lysis assays, and the best candidate (1) provided approximately a 2.5-fold improvement over the current gold standard, TXA. Molecular docking and molecular dynamics were used to perform a structure–activity relationship (SAR) analysis with the lysine binding site in the Kringle 1 domain of plasminogen. This analysis revealed that 1,2,3-triazole was crucial for the activity, enhancing the binding affinity through pi–pi stacking and polar interactions with Tyr72. The results presented in this work open the door to further investigate this new family as potential antifibrinolytic drugs.


 
45 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 14945: Coordination of the AMPK, Akt, mTOR, and p53 Pathways under Glucose Starvation (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 14944: CRISPR/Cas9-Mediated Targeted Mutagenesis of BnaCOL9 Advances the Flowering Time of Brassica napus L. (International Journal of Molecular Sciences)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Molecular Biology


Copyright © 2008 - 2023 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Nachrichten