Panquinone - Liquid Triquinoyl/Quinone Mix For Lab/R&D

Philomath

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This email quote from Dr. Peat appears to be somewhat contradictory, especially in regards to Methylglyoxal

“Chris Masterjohn has written some good articles on cholesterol, but this one isn’t so good. The fact that, under extreme conditions, some fat is converted into glucose, doesn’t make ketosis less harmful; most of the glucose is still coming from tissue proteins, and the pathway they identify, through methylglyoxal, just helps to explain some of the long-range harm done by ketosis, since methylglyoxal made from the glycerol released when tissue triglycerides are metabolized is (along with acrolein and other lipid peroxidation products) a major factor in the degenerative changes produced by diabetic ketosis, or by the increased free fatty acid metabolism caused by trauma. Any extra methylglyoxal from fatty acid conversion adds to the effect of that from triglyceride metabolism and any from lactic acid, to accelerate aging, autoimmunity, neurological degeneration, etc.”
 
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Braveheart

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I'm mostly raw vegan, but not for any sort of . . . reasons dealing with empathy. I like animals—mostly squirrels—but not so much chickens or cows. It doesn't particularly bother me when people kill chickens (but please brake for squirrels).

I smoke cigarettes, and drink a veritable ***t‐ton of coffee.

But drawing the line between just vegan and not vegan isn't too helpful, in terms of health. There are so many crappy vegan foods like canola oil (a.k.a. prostaglanin precursors), wheat (prolactin stimulator), and refined sugar (tending to deplete B vitamins). I think a better line would be towards whole foods, of any type—with whole raw foods going further yet. That's not to say that all cooked foods are bad, but there seems to be a trend . . . and they can be addictive.

I would vote for refined wheat flour as the worst possible thing to eat. Wheat products have: reduced iron, gluten, and sometimes even aluminum from the double‐acting baking powder.
Thanks, I agree
 

Obi-wan

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Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, Black turtle bean[9] and Sesame seeds.[10]

I think we would get enough in out diet. I do not eat lentils, beans, or sesame. I have tried Pau'Darco Tea. I get much better results with Lapodin. I now try to be careful with PUFA intake. Drinking chicken bone broth from the farm made it worse. Fish oil made it worse (before I knew Peat). Flackseed made it worse (before I knew Peat). Also DIM, oral DHEA, Boron made it worse(before I knew Peat) I feel my prostate cancer in my ribs and neck. Since it is close to my ears I can also hear it at times. It sings at a higher frequency sometimes oscillating. I wonder if it is signaling other cells? This usually starts in the afternoon after lunch and ends later in the evening. @bzmazu welcome to the party. I tend to eat towards whole foods and like raw milk from the farm. I like @haidut's Vit K.
 
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Braveheart

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Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, Black turtle bean[9] and Sesame seeds.[10]

I think we would get enough in out diet. I do not eat lentils, beans, or sesame. I have tried Pau'Darco Tea. I get much better results with Lapodin. I now try to be careful with PUFA intake. Drinking chicken bone broth from the farm made it worse. Fish oil made it worse (before I knew Peat). Flackseed made it worse (before I knew Peat). Also DIM, oral DHEA, Boron made it worse(before I knew Peat) I feel my prostate cancer in my ribs and neck. Since it is close to my ears I can also hear it at times. It sings at a higher frequency sometimes oscillating. I wonder if it is signaling other cells? This usually starts in the afternoon after lunch and ends later in the evening. @bzmazu welcome to the party. I tend to eat towards whole foods and like raw milk from the farm. I like @haidut's Vit K.

Obi-wan, we are on the same page...I follow your posts w much interest.
 

Travis

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Obi-wan, we are on the same page...I follow your posts w much interest.
Diabetics have enough methylglyoxal in their blood to have measurably higher serum albumin fluorescence.

But I think it could have signalling functions, by creating a the post‐translational modifications on proteins (see Thornally). When it's made extracellularly—as in diabetes where the glucose is found higher extracellularly—it's likely more problematic because collagen has a lower turnover rate than most cells. When produced inside of the cell in a person not diabetic, then the glutathione and glyoxylase will keep things in order.

It's easy to see methylglyoxal as pathological when its extracellular role in the case of diabetes is the primary focus.
 

Obi-wan

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"Recently, Schug et al. showed that when the cellular retinoic acid binding protein-II (CRABP-II) expression levels were higher than FABP5 in the cells, retinoic acid (RA) bound to CRABP- II. Subsequently, CRABP-II relocated to the nucleus and delivered RA to RAR, resulting in inhibition of cell proliferation and induction of apoptosis. On the contrary, when the FABP5 to CRABP-II ratio is high, RA serves as a physiological ligand for PPARδ, which induces cell survival and proliferation. Therefore, it is important to identify the cytosolic ligand binding proteins and the expression levels of the proteins for defining the physiological effects of ligands.

The Role of PPARs in Cancer

Wow hard to read but this is what I got out of it:

Epidemiological studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, indomethacin, and sulindac, reduce the overall number and size of adenomas in patients with FAP. Healthy individuals using NSAIDs regularly can lead to a 40–50% reduction in the relative risk of developing colon cancer [90]. NSAIDs inhibit cyclooxygenase (COX) activity and thereby reduce prostaglandin synthesis [91]. COX is a key enzyme in arachidonic acid metabolism and prostaglandin production. COX catalyzes a two-step reaction that converts arachidonic acid to prostaglandin H2 (PGH2), which in turn serves as the precursor for the synthesis of all biologically active prostaglandins, including PGD2, PGE2, PGF2 α, prostacyclin (PGI2), and thromboxane A2 (TXA2) [92]. COX exists in two isoforms that are encoded by two separate genes. COX-1 is constitutively expressed in most tissues, on the other hand, the expression of COX-2 is normally low or absent in most tissues but is rapidly upregulated by proinflammatory cytokines [93]. Expression of COX-2 is also elevated in colorectal cancer and in a subset of adenomas [94]. Moreover, since both the introduction of the knockout mutation of the COX-2 gene into A p c Δ716 mice, a model of human FAP, and treating A p c Δ716 mice with NSAIDs reduce the development of intestinal tumors, COX-2 inhibitors have been considered as therapeutic agents for colorectal polyposis and cancer [95]. He et al. reported that NSAIDs inhibited the transcriptional activity of PPARδ by disruption of the DNA binding ability of PPARδ/RXR heterodimers, and ectopic expression of PPARδ in the human colorectal cancer cell line, HCT116, protected the cells from sulindac-induced apoptosis [77]. PPARδ and COX-2 mRNA are expressed in similar regions in human colon cancer, and the stable PGI2 analog, carbaprostacyclin (cPGI), acts as a PPARδ ligand [11, 78]. Indeed, ectopic expression of COX-2 and PGI synthase (PGIS) in the human osteosarcoma cell line, U2OS, produced high levels of endogenous PGI2 and transactivation of PPARδ [78]. PGE2 levels are also elevated in human colorectal cancers and adenomas, and PGE2 increases the growth and motility of colorectal carcinoma cells [96, 97]. D. Wang et al. showed that PGE2 promoted resistance to serum starvation-induced apoptosis of cultured human colon carcinoma cells, LS-174T, through indirectly upregulation PPARδ transcriptional activity via a phosphotidylinositol-3-kinase (PI3K)-Akt pathway [98]. Furthermore, PGE2 accelerates intestinal adenoma growth of A p c min mice, a model of human FAP that harbors a mutation in the apc gene, via PPARδ [98]. Xu et al. showed that PGE2 activated cytosolic phospholipase A2 α (cPLA2 α) through PI3K or MAPK pathway, and subsequently cPLA2 α enhanced PPARδ activity in the human cholangiocarcinoma cells [99]. They also showed that PPARδ enhanced COX2 expression and PGE2 production. This positive feedback loop may play an important role in cholangiocarcinoma cell growth, although it is not known whether this kind of positive feedback loop exists in the colorectal cancer cells [99]. Thus PPARδ induces the cell proliferation through the inhibition of apoptosis. However, sulindac sulfide induces apoptosis not only in wild-type HCT116, but also in HCT116 PPARδ-null cell lines [100]. On the basis of these observations, although NSAIDs may reduce tumorigenesis through the inhibition of PPARδ activity, PPARδ is not a major mediator of sulindac-mediated apoptosis


ASPIRIN inhibits cyclooxygenase (COX) activity and thereby reduce prostaglandin synthesis.

Furthermore, NSAIDs increase 15-LOX-1 protein expression and its product 13-S-HODE levels and downregulate PPARδ expression in association with subsequent growth inhibition and apoptosis [106, 107]. Thus it is considered possible that PPARδ promotes the growth of colon cancers.

Prostaglandins, synthesized via the COX pathway from arachidonic acid, are released outside the cells and lead to changes in the cellular levels of cyclic AMP and Ca2+ through binding to G-protein-coupled receptors on the plasma membrane

ASPIRIN can reduce the level of Ca2+ inside the cell.

Cancer cells represent dysregulaton of the cell cycle and lead to cell proliferation. In this viewpoint, modulators of the cell cycle and/or apoptosis are useful as chemotherapeutic agents for cancer [126, 127]. A number of investigators have shown that PPARγ was expressed in a variety of tumor cells, and the activation of PPARγ by ligands led to either inhibition of cell proliferation or induction of apoptosis

Moreover, PPARγ ligand showed antitumor effect against human prostate cancer cells and human lung cancer cells [143, 144, 171173]. Thus PPARγ ligands could suppress the tumorigenesis. Therefore, PPARγ ligands could be used as antineoplastic drugs.

Furthermore, recent evidence suggests that the ligand binding protein in the cytosol that transports ligands into the nucleus is important to modulate the action of nuclear receptors. Long-chain fatty acids, endogenous PPAR ligands, are highly hydrophobic and fatty acids are bound to fatty acid binding proteins (FABPs) in the aqueous intracellular compartment [182]. FABPs also bind to PPAR ligands and transport them from the cytosol into the nucleus [183191]. In the nucleus, FABPs interact directly with PPARs and deliver ligands to PPARs, and the activity of PPARs is modulated

Is this a case for saturated fatty acids?
 

Obi-wan

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@Travis, looks like PPAR's have been a popular topic of yours on other posts as well
 

Travis

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@Travis PPARδ and COX-2 mRNA are expressed in similar regions in human colon cancer, and the stable PGI₂ analog, carbaprostacyclin (cPGI), acts as a PPARδ ligand
Nice, you found the natural PPARδ ligand; I was looking for that.

The PPARs certainly appear to be the fat‐sensing receptors, responding most strongly to the prostaglandins. From what I've read, all of them appear to be anabolic and increase growth.

But prostaglandin D₂ can act in another important way: first by spontaneously becoming prostaglandin J₂, which then goes‐on to release p53.

prostaglandin D₂ ⟶ prostaglandin J₂ + H₂O

The interaction between prostaglandin J₂ and p53 can be seen as a big deal. The p53 transcription factor can have a powerful effect on the cell.

The upregulation of prostaglandin D₂ synthase appears to be under the control of cortisol, acting through SOX9, explaining why males have both more of this enzyme and its product—prostaglandin D₂. After prostaglandin H₂ is formed, there seems to be no reliable way of knowing exactly the ratios in which these downstream prostaglandins will be formed (except of course by knowing what you can't possibly: the exact ratio of the enzymes within the cell.) What perhaps could be best is be finding out how to shift the ratios of these enzymes—but this would be difficult. Much easier is limiting linoleic acid and using COX‐2 inhibitors until much of the arachidonic acid is safely metabolized through cell turnover. This is what I'm going to do; I went on an almond binge for a few weeks when my grocery store was out of coconuts—but now I'm back on coconuts.

The way prostaglandins interact with G‐protein‐coupled receptors is even more esoteric than their effects on DNA transcription, and seems just as hard to comprehend. But microtubules, and the G‐protein‐coupled receptors they attach to, are very interesting.

The 'niacin flush' is commonly explained through the interaction of prostaglandin E₂, niacin, prostaglandin D₂, and a G‐protein‐coupled receptor. I think finding out exactly how it does so would go a long way towards understanding the cytosolic effects of prostaglandins. I have some ideas about G‐protein‐coupled receptors by they're quite non‐conventional.
 

Obi-wan

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I agree, PPAR's are definitely fat sensing receptors and depending on the type of fat different ligands will be activated. P53 is the apoptosis gene. In my case I want it activated. Any thoughts on activation. I know estrogen deactivates it.
 
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Why is it that in glaucoma they have drops that agonize prostaglandin "receptors"

Clinical appraisal of tafluprost in the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension

glaucoma drops prostaglandins.jpg
 

Travis

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Why is it that in glaucoma they have drops that agonize prostaglandin "receptors"
That's a good question. I know the first studies showing prostaglandin‐induced 'hair growth was one with prostaglandin F₂α—or was is lantaprost?—on eyelashes. Sure, it lengthens eyelashes, but how can anyone justify putting a prostaglandin analogue in their eye?

I also would like to know why they do this.
I agree, PPAR's are definitely fat sensing receptors and depending on the type of fat different ligands will be activated. P53 is the apoptosis gene. In my case I want it activated. Any thoughts on activation. I know estrogen deactivates it.
I'm not sure if there's a safe way of going about that. I'm still of the opinion that methylglyoxal and Gerson are the two things most worthy of attention.

The p53 sits inactive in a binding protein called MDM2. Judging by its extensive thiol domain, and how prostaglanind J₂ activates it, I got the impression that it naturally senses redox status. I see it as a 'doomsday switch' within the nucleus released upon conditions of altered redox status, normally causing the cell to self‐destruct when the cell is not producing energy.
 

Koveras

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I agree, PPAR's are definitely fat sensing receptors and depending on the type of fat different ligands will be activated. P53 is the apoptosis gene. In my case I want it activated. Any thoughts on activation. I know estrogen deactivates it.

I'm not sure if there's a safe way of going about that. I'm still of the opinion that methylglyoxal and Gerson are the two things most worthy of attention.

The p53 sits inactive in a binding protein called MDM2. Judging by its extensive thiol domain, and how prostaglanind J₂ activates it, I got the impression that it naturally senses redox status. I see it as a 'doomsday switch' within the nucleus released upon conditions of altered redox status, normally causing the cell to self‐destruct when the cell is not producing energy.

Interleukin-6 interferes with p53 function, and interleukin-6 is increased by prolactin (and vice versa) - so that might be another case for a dopamine agonist.

Hodge, D. R., Peng, B., Cherry, J. C., Hurt, E. M., Fox, S. D., Kelley, J. A., . . . Farrar, W. L. (2005). Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res, 65(11), 4673-4682. doi:10.1158/0008-5472.CAN-04-3589​

Berberine (a PPARy agonist) has some interesting research around it

Qing, Y., Hu, H., Liu, Y., Feng, T., Meng, W., Jiang, L., . . . Yao, Y. (2014). Berberine induces apoptosis in human multiple myeloma cell line U266 through hypomethylation of p53 promoter. Cell Biol Int, 38(5), 563-570.

Mutat Res. 2009 Mar 9;662(1-2):75-83. doi: 10.1016/j.mrfmmm.2008.12.009. Epub 2008 Dec 31.
Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage.
Liu Z1, Liu Q, Xu B, Wu J, Guo C, Zhu F, Yang Q, Gao G, Gong Y, Shao C.

Int J Clin Pharmacol Ther. 2017 Jan;55(1):32-40. doi: 10.5414/CP202534.
Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest
.
Zhuo Y, Chen Q, Chen B, Zhan X, Qin X, Huang J, Lv X.

Int J Oncol. 2016 Jul;49(1):411-21. doi: 10.3892/ijo.2016.3502. Epub 2016 Apr 26.
Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α.
Park GB1, Park SH2, Kim D3, Kim YS3, Yoon SH4, Hur DY3.

Biochem Biophys Res Commun. 2014 Jul 18;450(1):697-703. doi: 10.1016/j.bbrc.2014.06.039. Epub 2014 Jun 16.
Mitochondrial protein cyclophilin-D-mediated programmed necrosis attributes to berberine-induced cytotoxicity in cultured prostate cancer cells.
Zhang LY1, Wu YL1, Gao XH1, Guo F2.

Mutat Res. 2012 Jun 1;734(1-2):20-9. doi: 10.1016/j.mrfmmm.2012.04.005. Epub 2012 Apr 26.
Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells.
Wang Y1, Liu Q, Liu Z, Li B, Sun Z, Zhou H, Zhang X, Gong Y, Shao C.

Int J Biol Sci. 2017 Jun 1;13(6):794-803. doi: 10.7150/ijbs.18969. eCollection 2017.
Berberine Reverses Hypoxia-induced Chemoresistance in Breast Cancer through the Inhibition of AMPK- HIF-1α.
Pan Y1, Shao D1, Zhao Y1, Zhang F1, Zheng X1, Tan Y1, He K1, Li J1, Chen L1,2.

J Cancer. 2017 Jun 5;8(9):1679-1689. doi: 10.7150/jca.19106. eCollection 2017.
Berberine Enhances Chemosensitivity and Induces Apoptosis Through Dose-orchestrated AMPK Signaling in Breast Cancer.
Pan Y1, Zhang F1, Zhao Y1, Shao D1,2, Zheng X1, Chen Y1, He K1, Li J1, Chen L1,3.​

Int J Oncol. 2009 May;34(5):1221-30.
Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells.
Choi MS1, Oh JH, Kim SM, Jung HY, Yoo HS, Lee YM, Moon DC, Han SB, Hong JT.​

As well as curcumin ...if you can get it into the cells it needs to affect as Travis has alluded to.

Li, W., Wang, Y., Song, Y., Xu, L., Zhao, J., & Fang, B. (2015). A preliminary study of the effect of curcumin on the expression of p53 protein in a human multiple myeloma cell line. Oncol Lett, 9(4), 1719-1724. doi:10.3892/ol.2015.2946​
 

Obi-wan

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Berberine is known to inhibit CYP2D6, CYP2C9, and CYP3A4, which can lead to a host of drug interactions, some of which can be serious. Enzalutamide is an inducer of CYP3A4, CYP2C9, and CYP3A4 and is metabolized by CYP2C8 and CYP3A4. Looks like interaction to me. Hate to waste a $97,000 a month drug ($20 co-pay) Probably should stick with the apoptosis from Enzalutamide
 

Koveras

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Berberine is known to inhibit CYP2D6, CYP2C9, and CYP3A4, which can lead to a host of drug interactions, some of which can be serious. Enzalutamide is an inducer of CYP3A4, CYP2C9, and CYP3A4 and is metabolized by CYP2C8 and CYP3A4. Looks like interaction to me. Hate to waste a $97,000 a month drug ($20 co-pay) Probably should stick with the apoptosis from Enzalutamide

Probably not worth the risk - but whether's it's a waste of money will depend on how the drug is metabolized. If it's the enzalutamide parent molecule that's active, and it's metabolized by CYP3A4 - and berberine inhibits that to a degree - then that could lead to higher blood levels of the drug and potentially increased effectiveness for a given dose. Of course, increased toxicity as well.
 

Obi-wan

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Thanks @Koveras . There is a potential for stroke on this drug. I do take emodin and Pau D'Arco via Lapodin and do not see any interactions. Thoughts?
 
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haidut

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Thanks @Koveras . There is a potential for stroke on this drug. I do take emodin and Pau D'Arco via Lapodin and do not see any interactions. Thoughts?

Hey peeps, much appreciate the discussion but can we start a separate thread on this please? This is not related to Panquinone or William Koch and I wanted to keep this thread focused on that as much as possible.
Thanks in advance.
 

LemonT

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Hey peeps, much appreciate the discussion but can we start a separate thread on this please? This is not related to Panquinone or William Koch and I wanted to keep this thread focused on that as much as possible.
Thanks in advance.
Hi Haidut,

Please excuse my ignorance but in a podcast I heard you say that quinones are things like vitamin k and the myno or tetra family of antibiotics. Is this product similar to that? Can it hypothetically do the same thing? Does it have action against bacteria and serotonin if given to rats?

I've got a lot more reading to do but just curious.
 
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haidut

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Hi Haidut,

Please excuse my ignorance but in a podcast I heard you say that quinones are things like vitamin k and the myno or tetra family of antibiotics. Is this product similar to that? Can it hypothetically do the same thing? Does it have action against bacteria and serotonin if given to rats?

I've got a lot more reading to do but just curious.

It does contains quinones, and the triquinoyl is supposed to be one of the most powerful quinones there is. I don't know if it has anti-bacterial effects as there have been very few studies with it but most quinones do, so I would not be surprised if it does as well.
 

aguilaroja

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...Does it have action against bacteria and serotonin if given to rats?
It does contains quinones, and the triquinoyl is supposed to be one of the most powerful quinones there is. I don't know if it has anti-bacterial effects as there have been very few studies with it but most quinones do, so I would not be surprised if it does as well.

Anti-Bacterial Activity of Phenolic Compounds against Streptococcus pyogenes
“…1,2-naphthoquinone and 5-hydroxy-1,4-naphthoquinone inhibit S. pyogenes and should be further investigated as candidates for the management of streptococcal pharyngitis.”

Searching for a potential antibacterial lead structure against bacterial biofilms among new naphthoquinone compounds. - PubMed - NCBI
“After probing 36 naphthoquinones for a potential antibacterial lead structure against the bacterial biofilm, we found that compound 15 should be explored further and also should be structurally modified in the near future to test against Gram-negative strains.”
 
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haidut

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Anti-Bacterial Activity of Phenolic Compounds against Streptococcus pyogenes
“…1,2-naphthoquinone and 5-hydroxy-1,4-naphthoquinone inhibit S. pyogenes and should be further investigated as candidates for the management of streptococcal pharyngitis.”

Searching for a potential antibacterial lead structure against bacterial biofilms among new naphthoquinone compounds. - PubMed - NCBI
“After probing 36 naphthoquinones for a potential antibacterial lead structure against the bacterial biofilm, we found that compound 15 should be explored further and also should be structurally modified in the near future to test against Gram-negative strains.”

Thanks. Now we have more specific evidence. I think the benzoquinones (BQ), and especially the "naked" BQ like 14,benzoquinone and 1,2-benzoquinone are also quite potent antibacterials. William Koch got his idea of using them for all kinds of disease by first observing how potent they were as antibiotics, with few side effects when used at the proper dose.
 

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