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.
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