Ornithine is a non-proteinogenic α-amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.
Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against Gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against Gram-positive bacilli and anaerobic Gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds.
β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.
Physostigmine is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree.
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages it can result in a coma.
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease, and indicates that the liver has sustained severe damage. The complications are hepatic encephalopathy and impaired protein synthesis. The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.
Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is administered orally for constipation, and either orally or rectally for hepatic encephalopathy. It generally begins working after 8–12 hours, but may take up to 2 days to improve constipation.
The Martinet dioxindole synthesis was first reported in 1913 by J. Martinet. It is a chemical reaction in which a primary or secondary aniline or substituted aromatic amine is condensed with ethyl or methyl ester of mesoxalic acid to make a dioxindole in the absence of oxygen.
Isatin, also known as tribulin, is an organic compound derived from indole with formula C8H5NO2. The compound was first obtained by Otto Linné Erdman and Auguste Laurent in 1840 as a product from the oxidation of indigo dye by nitric acid and chromic acids.
Isoindoline is a heterocyclic organic compound with the molecular formula C8H9N. The parent compound has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing ring. The compound's structure is similar to indoline except that the nitrogen atom is in the 2 position instead of the 1 position of the five-membered ring. Isoindoline itself is not commonly encountered, but several derivatives are found in nature and some synthetic derivatives are commercially valuable drugs, e.g. lenalidomide and pazinaclone.
Semaxanib is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential.
Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today: topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.
The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it.
Strictosidine synthase (EC 4.3.3.2) is an enzyme in alkaloid biosynthesis that catalyses the condensation of tryptamine with secologanin to form strictosidine in a formal Pictet–Spengler reaction:
Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They are selective 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine.
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is a condition of the liver in which the normal functioning tissue, or parenchyma, is replaced with scar tissue (fibrosis) and regenerative nodules as a result of chronic liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regenerating hepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver's capillaries—the hepatic sinusoids—and consequently portal hypertension, as well as impairment in other aspects of liver function. The disease typically develops slowly over months or years.
Indole is an organic compound with the formula C6H4CCNH3. Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole where one or more of the hydrogen atoms have been replaced by substituent groups. Indoles are widely distributed in nature, most notably as amino acid tryptophan and neurotransmitter serotonin.
MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb, that acts as a reasonably selective agonist of peripheral cannabinoid receptors. It has moderate affinity for CB2 receptors with a Ki of 11 nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8 nM at CB1 and 29 nM at CB2, which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB2 (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).
Substituted tryptamines, or serotonin analogues, are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.
Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida, Vinca minor and the Aspidosperma.
