New Blood Coagulation Factor XIIa Inhibitors: Molecular Modeling, Synthesis, and Experimental Confirmation

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Feb 25

PMID 35209023

Authors

Anna Tashchilova

Nadezhda Podoplelova

Alexey Sulimov

Danil Kutov

Ivan Ilin

Mikhail Panteleev

Khidmet Shikhaliev

Svetlana Medvedeva

Nadezhda Novichikhina

Andrey Potapov

Vladimir Sulimov

Affiliations

Soon will be listed here.

Abstract

In the modern world, complications caused by disorders in the blood coagulation system are found in almost all areas of medicine. Thus, the development of new, more advanced drugs that can prevent pathological conditions without disrupting normal hemostasis is an urgent task. The blood coagulation factor XIIa is one of the most promising therapeutic targets for the development of anticoagulants based on its inhibitors. The initial stage of drug development is directly related to computational methods of searching for a lead compound. In this study, docking followed by quantum chemical calculations was used to search for noncovalent low-molecular-weight factor XIIa inhibitors in a focused library of druglike compounds. As a result of the study, four low-molecular-weight compounds were experimentally confirmed as factor XIIa inhibitors. Selectivity testing revealed that two of the identified factor XIIa inhibitors were selective over the coagulation factors Xa and XIa.

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