Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3

Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3 Full article

Journal

Molecules
ISSN: 1420-3049

Output data

Year: 2023, Volume: 28, Number: 8, Article number : 3568, Pages count : DOI: 10.3390/molecules28083568

Authors

Potapov Konstantin V. ^1,2 , Novikov Roman A. ^3,1,2 , Novikov Maxim A. ² , Solyev Pavel N. ¹ , Tomilov Yury V. ² , Kochetkov Sergey N. ¹ , Makarov Alexander A. ¹ , Mitkevich Vladimir A. ¹

Affiliations

1	Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences, 32 Vavilov St., 119991 Moscow, Russia
2	Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, 47 Leninsky Avenue, 119991 Moscow, Russia
3	Biotechnology Department, Sirius University of Science and Technology, 1 Olympic Avenue, 354349 Sirius, Russia

Bacterial cystathionine γ-lyase (bCSE) is the main producer of H2S in pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, etc. The suppression of bCSE activity considerably enhances the sensitivity of bacteria to antibiotics. Convenient methods for the efficient synthesis of gram quantities of two selective indole-based bCSE inhibitors, namely (2-(6-bromo-1H-indol-1-yl)acetyl)glycine (NL1), 5-((6-bromo-1H-indol-1-yl)methyl)- 2-methylfuran-3-carboxylic acid (NL2), as well as a synthetic method for preparation 3-((6-(7-chlorobenzo[b]thiophen-2-yl)-1H-indol-1-yl)methyl)- 1H-pyrazole-5-carboxylic acid (NL3), have been developed. The syntheses are based on the use of 6-bromoindole as the main building block for all three inhibitors (NL1, NL2, and NL3), and the designed residues are assembled at the nitrogen atom of the 6-bromoindole core or by the substitution of the bromine atom in the case of NL3 using Pd-catalyzed cross-coupling. The developed and refined synthetic methods would be significant for the further biological screening of NL-series bCSE inhibitors and their derivatives.

Potapov K.V. , Novikov R.A. , Novikov M.A. , Solyev P.N. , Tomilov Y.V. , Kochetkov S.N. , Makarov A.A. , Mitkevich V.A.
Synthesis of the Indole-Based Inhibitors of Bacterial Cystathionine γ-Lyase NL1-NL3
Molecules. 2023. V.28. N8. 3568 . DOI: 10.3390/molecules28083568 WOS Scopus OpenAlex

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