Eupatorin is a natural flavonoid isolated from the herbs of Eupatorium semiserratum. It has the anti-inflammatory and anti-proliferative properties, which may be utilized in the development of novel anti-inflammatory and anti-tumor treatments. Eupatorin moderately inhibited human cytochrome P450 1A2 (CYP1A2). Eupatorin showed IC50 values of 0.4 ug/mL on T. cruzi epimastigotes and 61.8 ug/mL on trypomastigotes, respectively. It was demonstrated, that eupatorin exerts a vasorelaxative effect on aortic rings through the NO/sGC/cGMP and PGI2 pathways, calcium and potassium channels, muscarinic and beta-adrenergic receptors.

Coptisine (COP), a protoberberine alkaloid, is widely found in Chinese medicinal plants (family Berberidaceae, Ranunculaceae and Papaveraceae). It is reported that COP has a wide range of pharmacological and biological activities, including antibacterial, hypoglycemic, anti-tumorigenic, and gastric-mucous membrane protection. Considerable attention has been focused on its activity against central nervous system disorders, such as improving the symptoms of Alzheimer’s disease and even preventing its onset, by exerting antidepressant effects as a potent type A monoamine oxidase inhibitor. Coptisine was found to be an efficient uncompetitive Indoleamine 2,3-dioxygenase inhibitor. Coptisine is a potent inhibitor of human organic cation transporters.

N-Methyladenosine (m6A) is a methylated adenine residue and an endogenous urinary nucleoside product of the degradation of transfer ribonucleic acid (tRNA). Adenosine methylation is directed by a large m6A methyltransferase complex containing METTL3 as the SAM-binding sub-unit. In vitro, this methyltransferase complex preferentially methylates RNA oligonucleotides containing GGACU and a similar preference was identified in vivo in mapped m6A sites in Rous sarcoma virus genomic RNA and in bovine prolactin mRNA. More recent studies have characterized other key components of the m6A methyltransferase complex in mammals, including METTL14, Wilms tumor 1 associated protein (WTAP) and KIAA1429. Following a 2010 speculation of m6A in mRNA being dynamic and reversible, the discovery of the first m6A demethylase, fat mass and obesity-associated protein (FTO) in 2011 confirmed this hypothesis and revitalized the interests in the study of m6A. A second m6A demethylase alkB homolog 5 (ALKBH5) was later discovered as well. The biological functions of m6A are mediated through a group of RNA binding proteins that specifically recognize the methylated adenosine on RNA. These binding proteins are named m6A readers. The YT521-B homology (YTH) domain family of proteins (YTHDF1, YTHDF2, YTHDF3, and YTHDC1) have been characterized as direct m6A readers and have a conserved m6A-binding pocket. These m6A readers, together with m6A methyltransferases (writers) and demethylases (erasers), establish a complex mechanism of m6A regulation in which writers and erasers determine the distributions of m6A on RNA, whereas readers mediate m6A-dependent functions. m6A has also been shown to mediate a structural switch termed m6A switch. Considering the versatile functions of m6A in various physiological processes, it is thus not surprising to find links between m6A and numerous human diseases; many originated from mutations or single nucleotide polymorphisms (SNPs) of cognate factors of m6A. The linkages between m6A and numerous cancer types have been indicated in reports that include stomach cancer, prostate cancer, breast cancer, pancreatic cancer, kidney cancer, mesothelioma, sarcoma, and leukemia. The depletion of METTL3 is known to cause apoptosis of cancer cells and reduce the invasiveness of cancer cells, while the activation of ALKBH5 by hypoxia was shown to cause cancer stem cell enrichment. m6A has also been indicated in the regulation of energy homeostasis and obesity, as FTO is a key regulatory gene for energy metabolism and obesity. SNPs of FTO have been shown to associate with body mass index in human populations and occurrence of obesity and diabetes. The influence of FTO on pre-adipocyte differentiation has been suggested. The connection between m6A and neuronal disorders has also been studied. For instance, neurodegenerative diseases may be affected by m6A as the cognate dopamine signaling was shown to be dependent on FTO and correct m6A methylation on key signaling transcripts. The mutations in HNRNPA2B1, a potential reader of m6A, have been known to cause neurodegeneration.

Blasticidin S is a metabolite of Streptomyces griseochromogenes and was formerly used in practice as a fungicide against a phytopathogenic fungus, Pyricularia oryzae. Blasticidin S inhibits protein synthesis of both prokaryotic and eukaryotic organisms by interacting with their ribosomes. Blasticidin S, a protein synthesis inhibitor, inhibits aflatoxin production of Aspergillus flavus without affecting fungal growth. It has been demonstrated that blasticidin S also exhibits antibacterial activity, toxicity to mammalians and tumor-inhibitory activity.

Ro 5-3335, 7-chloro-5-(2-pyrryl)-3H-1,4-benzo-diazepin-2-(H)-one, is a benzodiazepine compound. Originally Ro 5-3335 was shown to inhibit gene expression controlled by the human immunodeficiency virus-1 (HIV-1) LTR promoter. The inhibition was specific for the viral transcriptional transactivator Tat. The compound did not inhibit the basal activity of the HIV-1 LTR or the activity of promoters not responsive to Tat. In addition Ro 5-3335 was able to interact with RUNX1 and CBFβ directly, repress RUNX1/CBFB-dependent transactivation in reporter assays, and repress runx1-dependent hematopoiesis in zebrafish embryos. Ro5-3335 preferentially killed human CBF leukemia cell lines, rescued preleukemic phenotype in a RUNX1-ETO transgenic zebrafish, and reduced leukemia burden in a mouse CBFB-MYH11 leukemia model.

Digitonin is a steroidal saponin (saraponin) obtained from the foxglove plant Digitalis purpurea. As a non-ionic detergent Digitonin is commonly used to solubilize membrane-bound proteins. Digitonin forms a complex with its lipophilic terpenoid moiety with cholesterol in the biomembrane; additionally it binds to glycoproteins and glycolipids of the cell membrane with its sugar side chain. This leads to a severe tension of the biomembrane and influences membrane permeability. Digitonin, in combination with secondary metabolites, leads to a stronger inhibition of ABC transporters as when applied alone. Digitonin is used as a clinical reagent for the cholesterol determination. Digitonin mixed in the diet was well tolerated by rats and cynomolgus monkeys (Macaca fascicularis), and prevented the expected rise in plasma cholesterol in monkeys fed a diet containing butter and cholesterol.

Urethane (Ethyl carbamate) is is an ethyl ester of carbamic acid, that has been found in many fermented food products and alcoholic beverages such as cheese, bread, yogurt, wine, whiskey, soya sauce etc. An in vitro study indicated that Urethane has a potential to inhibit the growth of bacteria, plant tissue, and rat carcinoma. Urethane has been used for many years as an antineoplastic agent for medical purposes but this application ended after it was discovered to be carcinogenic in 1943. Urethane can produce long-lasting anesthesia without affecting blood gases or blood pressure, it has been used in acute studies. In earlier studies, Urethane was also used as a co-solvent for water-insoluble analgesic and sedative drugs in Japan. By US FDA regulations, ethyl carbamate has been withdrawn from pharmaceutical use. However, small quantities of ethyl carbamate are also used in laboratories as an anesthetic for animals.

Dibenzoylmethane (DBM), a minor ingredient in licorice, is a calcium chelator that binds calcium through the β-diketone moiety, and it has been found to increase intracellular calcium concentrations in skeletal muscle cells. Intracellular calcium regulates the binding of Nrf2 to the HO-1 enhancer region. Both Nrf2 and HO-1 have been proposed as potential drug targets to prevent or treat liver disease. Thus was suggested DBM could be a lead/candidate for prevention or treatment of liver diseases. In addition, was found, that dibenzoylmethane inhibits mammary tumorigenesis, lymphomas, and leukemias in mice and it can prevent the formation of tumor-inducing DNA adducts.

In mammalian as well as in plant DNA, and in the DNA of many other organisms, there occurs a fifth nucleotide, 5-methyldeoxycytidine (5-mC), in addition to the traditionally recognized four nucleotides A, C, G, and T. The modification of cytidine to 5-mC, apparently the only one among the nucleotides in mammalian DNA, is introduced postreplicationally by several DNA methyltransferases (DNMT) which are chosen depending on the functional context of their enzymatic activity: DNA can be methylated de novo, still a most enigmatic series of events, or a given pattern of DNA methylation in the genome can be maintained upon replication. In general, 5-mC can be considered as a modulator of protein-DNA interactions and genome activity.

Tetrahydrodiferuloylmethane (aka Tetrahydrocurcumin) is a bioactive metabolite of curcumin. It has been shown to have anti-inflammatory, anti-oxidant, anti-cancer, and neuroprotective effects in several in vitro and in vivo models. However, there have been no advances in human trials for these conditions. It should be noted that tetrahydrocurcumin is used in non-medicinal skin care formulations intended for skin whitening, skin soothing, and anti-oxidant effects.