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Volume 12
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10.3390/eca2022-12695
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Abstract

Structure–Activity Relationship for Natural Tetracenomycin X Congeners †

by
Vera A. Alferova
1,2,*,
Tinashe P. Maviza
3,
Mikhail V. Biryukov
2,4,5,
Yuliya V. Zakalyukina
5,6,
Dmitrii A. Lukianov
3,
Dmitry A. Skvortsov
7,
Lilia A. Vasilyeva
7,
Vadim N. Tashlitsky
7,
Vladimir I. Polshakov
7,
Petr V. Sergiev
3,7,
Ilya A. Osterman
3,5,7 and
Vladimir A. Korshun
1,2
1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow 117997, Russia
2
Gause Institute of New Antibiotics, Russian Academy of Sciences, Bolshaya Pirogovskaya 11, Moscow 119021, Russia
3
Center of Life Sciences, Skolkovo Institute of Science and Technology, Skolkovo 143028, Russia
4
Department of Biology, Moscow State University, GSP-1, Leninskie Gory, Moscow 119991, Russia
5
Genetics and Life Sciences Research Center, Sirius University of Science and Technology, Sochi 354340, Russia
6
Department of Soil Science, Moscow State University, GSP-1, Leninskie Gory, Moscow 119991, Russia
7
Department of Chemistry, Moscow State University, GSP-1, Leninskie Gory, Moscow 119991, Russia
*
Author to whom correspondence should be addressed.
†
Presented at the 2nd International Electronic Conference on Antibiotics—Drugs for Superbugs: Antibiotic Discovery, Modes of Action and Mechanisms of Resistance, 15–30 June 2022; Available online: https://eca2022.sciforum.net/.
Med. Sci. Forum 2022, 12(1), 21; https://doi.org/10.3390/eca2022-12695
Published: 15 June 2022
(This article belongs to the Proceedings of The 2nd International Electronic Conference on Antibiotics—Drugs for Superbugs: Antibiotic Discovery, Modes of Action and Mechanisms of Resistance)
Versions Notes

Abstract

:
The aromatic polyketide tetracenomycin X (TcmX) was recently found to be a potent inhibitor of protein synthesis; its binding site is located in a unique locus within the tunnel of the large ribosomal subunit. The distinct mode of action makes this relatively narrow class of aromatic polyketides promising for drug development in the quest to prevent the spread of drug-resistant pathogens. We isolated two novel tetracenomycin congeners: 6-hydroxytetracenomycin X (6-OH-TcmX) and O4-Me-Tcm C (TcmX isomer). Spectral properties of the compounds were studied. 6-OH-TcmX exhibited lower antimicrobial and cytotoxic activity, whereas the TcmX isomer was found to be completely inactive. Interestingly, the in vitro protein synthesis inhibition ability of TcmX and 6-OH-TcmX were found to be comparable, suggesting a significant influence of 6-hydroxylation on the tetracenomycin X cell penetration ability. The complete absence of both antimicrobial activity and the in vitro protein synthesis inhibition ability of the TcmX isomer corroborates the crucial role of the 4-OH group in ribosome binding.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/eca2022-12695/s1.

Author Contributions

Conceptualization, V.A.A., V.A.K. and I.A.O.; investigation, V.A.A., T.P.M., M.V.B., Y.V.Z., D.A.L., L.A.V., V.N.T. and V.I.P.; data analysis, V.A.A., D.A.S., V.I.P., P.V.S., V.A.K. and I.A.O.; conference presentation, V.A.A. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement No 075–15-2021-1049).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Alferova, V.A.; Maviza, T.P.; Biryukov, M.V.; Zakalyukina, Y.V.; Lukianov, D.A.; Skvortsov, D.A.; Vasilyeva, L.A.; Tashlitsky, V.N.; Polshakov, V.I.; Sergiev, P.V.; et al. Structure–Activity Relationship for Natural Tetracenomycin X Congeners. Med. Sci. Forum 2022, 12, 21. https://doi.org/10.3390/eca2022-12695

AMA Style

Alferova VA, Maviza TP, Biryukov MV, Zakalyukina YV, Lukianov DA, Skvortsov DA, Vasilyeva LA, Tashlitsky VN, Polshakov VI, Sergiev PV, et al. Structure–Activity Relationship for Natural Tetracenomycin X Congeners. Medical Sciences Forum. 2022; 12(1):21. https://doi.org/10.3390/eca2022-12695

Chicago/Turabian Style

Alferova, Vera A., Tinashe P. Maviza, Mikhail V. Biryukov, Yuliya V. Zakalyukina, Dmitrii A. Lukianov, Dmitry A. Skvortsov, Lilia A. Vasilyeva, Vadim N. Tashlitsky, Vladimir I. Polshakov, Petr V. Sergiev, and et al. 2022. "Structure–Activity Relationship for Natural Tetracenomycin X Congeners" Medical Sciences Forum 12, no. 1: 21. https://doi.org/10.3390/eca2022-12695

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