Mechanism of Action of Tetrocarcin A

Tamaok, Tatsuya; Tomita, Fusao; Obi, Yukiteru; Kawamura, Fujio; Saito, Hiuga

doi:10.1080/00021369.1983.10865585

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…It was shown that tetrocarcin A inhibited DDRP at nanomolar concentrations, but this was likely not the major mechanism of action. 17 This finding inspired us to screen lobophorins against M. tuberculosis , although the mechanism is probably not due to DDRP inhibition and requires testing. We found that the lobophorins are relatively potent: compounds 4 and 5 were about 4 x less potent than rifampicin control.…”

Section: Discussionmentioning

confidence: 99%

“…The antimycobacterial compound, rifampicin, works by inhibiting the DNA-dependent RNA polymerase (DDRP). 16 Since it was shown that a related compound also hit DDRP, 17 this led us to screen these compounds in assays against human cells and M. tuberculosis . Here, we describe novel compounds in the lobophorin series 18–20 with antimycobacterial activity.…”

Section: Introductionmentioning

confidence: 99%

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Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

et al. 2013

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A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1–5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis. A structure-activity relationship was discerned, wherein the lack of digitoxose in 1 led to lack of both cytotoxic and antibacterial activity. For compounds 2–5 both activities were in the low μM to mid nM range. Although this likely precludes their direct application in tuberculosis therapy due to possible poor therapeutic index, very slight changes in structure led to widely varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

et al. 2013

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“…Tetrocarcin A ( 51 , Figure 8) has been found to effectively inhibit Gram-positive bacteria by blocking RNA and protein synthesis [86]. In human cells, 51 was found to inhibit the integral intracellular membrane protein Bcl-2 and activate stress signals in the mitochondria and endoplasmic reticulum [44,87].…”

Section: Class II Marine Spirotetronatesmentioning

confidence: 99%

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Braddock

Theodorakis

2019

Marine Drugs

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Spirotetronates are actinomyces-derived polyketides that possess complex structures and exhibit potent and unexplored bioactivities. Due to their anticancer and antimicrobial properties, they have potential as drug hits and deserve further study. In particular, abyssomicin C and tetrocarcin A have shown significant promise against antibiotic-resistant S. aureus and tuberculosis, as well as for the treatment of various lymphomas and solid tumors. Improved synthetic routes to these compounds, particularly the class II spirotetronates, are needed to access sufficient quantities for structure optimization and clinical applications.

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Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein

et al. 2023

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Background The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro. Methods The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues. Results By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique. Conclusions The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.

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Mechanism of Action of Tetrocarcin A

Cited by 3 publications

References 4 publications

Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp

Marine Spirotetronates: Biosynthetic Edifices That Inspire Drug Discovery

Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein

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