Study of the effect of modification of the structure of a new derivative of quinazoline–4(3h)–one on fatty acid synthase (FAS) Mycobacterium

Relevance. Tuberculosis remains one of the main causes of disability and mortality from infectious diseases worldwide. The discovery of phenotypically tolerant subpopulations of pathogen persisters has called into question the possibilities of known anti-tuberculosis drugs. In this connection, the search and development of new effective anti-tuberculosis drugs is an important direction in the development of modern pharmacology. Currently, it is relevant to consider substances of the quinazoline nature as antimicrobial agents that exhibit antitubercular activity.

The aim of the work is computer modeling of the interaction of new derivatives of quinazoline–4(3H)–oh with NAD(H) in order to predict the possibility of influencing the fatty acid synthase (FAS) Mycobacterium.

Material and methods. Modeling of intermolecular complexes in the interaction system of new derivatives of quinazoline-4(3H)–on – VMA–17–04 and VMA–13–05 with the oxidized form of NAD⁺ was carried out using the quantum chemical semi-empirical PM7 method implemented in the MOPAC 2016 program.

Conclusions. The VMA–13–05 derivative, being in stable conformation I, forms an adduct with NAD⁺ having optimal energy characteristics. This interaction can be considered as one of the stages of the biochemical pathway of suppressing the activity of FAS synthase, which takes part in the synthesis of mycolic acids and leads to the death of Mycobacterium cells.