Alkaloids

by Fahry Marewo5

From Wikipedia, the free encyclopedia

This article is about the chemical compounds alkaloids. For the pharmaceutical company in the Republic of Macedonia, see Alkaloid (company).

Alkaloids are naturally occurring chemical compounds containing basic nitrogen atoms.[1] The name derives from the word alkaline and was used to describe any nitrogen-containing base. Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of the group of natural products (also called secondary metabolites). Many alkaloids can be purified from crude extracts by acid-base extraction. Many alkaloids are toxic to other organisms. They often have pharmacological effects and are used as medications, as recreational drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant cocaine, the stimulant caffeine, nicotine, the analgesic morphine, or the antimalarial drug quinine. Some alkaloids have a bitter taste.

Alkaloid classifications
Generally speaking, alkaloids are categorized under three main categories,depending on their biogenic origin. For those containing at least a nitrogen atom in a ring system derived from amino acids (i.e. alkaloids derived from phenylalanine are not grouped in this category), they are true alkaloids. The alkaloids derived from phenylalanine are categorized as protoalkaloids. While the remaining ones, such as steroidal alkaloids and purine alkaloids, are classified as pseudoalkaloids.
Alkaloids are usually classified by their common molecular precursors, based on the metabolic pathway used to construct the molecule.[citation needed] When not much was known about the biosynthesis of alkaloids, they were grouped under the names of known compounds, even some non-nitrogenous ones (since those molecules' structures appear in the finished product; the opium alkaloids are sometimes called "phenanthrenes", for example), or by the plants or animals they were isolated from. When more is learned about a certain alkaloid, the grouping is changed to reflect the new knowledge, usually taking the name of a biologically-important amine that stands out in the synthesis process.[original research?]
• Pyridine group: piperine, coniine, trigonelline, arecoline, arecaidine, guvacine, cytisine, lobeline, nicotine, anabasine, sparteine, pelletierine.
• Pyrrolidine group: hygrine, cuscohygrine, nicotine
• Tropane group: atropine, cocaine, ecgonine, scopolamine, catuabine
• Indolizidine group: senecionine, swainsonine
• Quinoline group: quinine, quinidine, dihydroquinine, dihydroquinidine, strychnine, brucine, veratrine, cevadine
• Isoquinoline group: opium alkaloids (papaverine, narcotine, narceine, morphine, codeine, heroine), sanguinarine, hydrastine, berberine, emetine, berbamine, oxyacanthine
• Phenanthrene alkaloids: opium alkaloids (morphine, codeine, thebaine)
• Phenethylamine group: mescaline, ephedrine, dopamine
• Indole group:
o Tryptamines: serotonin, DMT, 5-MeO-DMT, bufotenine, psilocybin
o Ergolines (the ergot alkaloids): ergine, ergotamine, lysergic acid
o Beta-carbolines: harmine, harmaline, tetrahydroharmine
o Yohimbans: reserpine, yohimbine
o Vinca alkaloids: vinblastine, vincristine
o Kratom (Mitragyna speciosa) alkaloids: mitragynine, 7-hydroxymitragynine
o Tabernanthe iboga alkaloids: ibogaine, voacangine, coronaridine
o Strychnos nux-vomica alkaloids: strychnine, brucine
• Purine group:
o Xanthines: caffeine, theobromine, theophylline
• Terpenoid group:
o Aconitum alkaloids: aconitine
o Steroid alkaloids (containing a steroid skeleton in a nitrogen containing structure):
 Solanum (e.g. potato and tomato) alkaloids (solanidine, solanine, chaconine)
 Veratrum alkaloids (veratramine, cyclopamine, cycloposine, jervine, muldamine)[2]
 Fire Salamander alkaloids (samandarin)
 Others: conessine
• Quaternary ammonium compounds: muscarine, choline, neurine
• Miscellaneous: capsaicin, cynarin, phytolaccine, phytolaccotoxin

Physicochemical properties
Low-molecular weight alkaloids without hydrogen bond donors such as hydroxy groups are often liquid at room temperature, examples are nicotine, sparteine, coniine, and phenethylamine.
The basicity of alkaloids depends on the lone pairs of electrons on their nitrogen atoms. As organic bases, alkaloids form salts with mineral acids such as hydrochloric acid and sulfuric acid and organic acids such as tartaric acid or maleic acid. These salts are usually more water-soluble than their free base form.

Aeromonas hydrophila

Aeromonads are ubiquitous, oxidase-positive, facultatively anaerobic, glucose-fermenting, Gram-negative bacteria that are native to aquatic environments (Hazen et al., 1978). They have been found in brackish, fresh, estuarine, marine, chlorinated and unchlorinated water supplies worldwide, with highest numbers obtained in the warmer months (Van der Kooj et al., 1988; Kaper et al., 1981; Hazen et al., 1978). Aeromonads have been isolated from diseased cold- and warm-blooded animals for over 100 years, and from humans since the early 1950s (Mathewson and Dupont, 1992).

Scanning electron micrograph of Aeromonas hydrophila attached to a human intestinal epithelial cell line (photo courtesy of Northwest Fisheries Science Center, NOAA).
Aeromonas hydrophila
• motile rod-shaped bacterium
• 0.3-1.0 um in diameter and 1.0-3.5 um in length
• no spore stage; usually unencapsulated
• optimum growth at 28 C, but growth observed at extremes (4 C and 37 C)

The ubiquitous nature of Aeromonas species in aquatic environments provides ample opportunity for animals, particularly fish and amphibians, to come into contact with, and to ingest organisms. Such contact may lead to infection which, depending on the species and the virulence of the strains encountered, may have life-threatening consequences.

Aeromonas hydrophila has been recovered from a wide-range of freshwater fish species worldwide, and occasionally from marine fish—e.g. ulcer disease of cod (Larsen and Jensen, 1977). However, conflicting views have been expressed over the precise role of A. hydrophila as a fish pathogen. Some researchers contend that the organism is only a secondary invader of previously weakened hosts, while others believe that A. hydrophila is a primary pathogen of freshwater fish (Eurell et al., 1978).
The Disease (in Fish)

A. hydrophila has been associated with several disease conditions in fish, including tail rot, fin rot, and haemorrahagic septicaemias. Haemorrahagic septicaemia is characterized by the presence of small surface lesions, often leading to sloughing off of the scales, haemorrhaging in the gills and anus, ulcers, abscesses, exophthalmia (bulging eyes), and abdominal swelling (dropsy)--often seen in European carp culture. Internally, there may be the presence of ascitic fluid in the peritoneal cavity, anaemia, and swelling of the kidney and liver (Miyazaki and Kaige, 1985). Another condition caused by A. hydrophila, known as red-fin disease, is characterized by the presence of surface haemorrhages and scale erosion.

Eel (Anguilla japonica) with red-fin disease caused by Aeromonas hydrophila (photo courtesy of Dr. Teruo Miyazaki). During the 1960s, outbreaks of red-fin disease, caused by A. hydrophila, occurred frequently in cultured eels in Japan (Hoshina, 1962; Egusa, 1978).

The etiologic agent is transmitted horizontally (between animals other than parents and offspring) but not vertically (from parent to offspring). The bacteria multiply inside the intestine, causing a haemorrhagic mucuous-desquamative catarrh (excessive mucous secretion). Toxic metabolites of A. hydrophila are absorbed from the intestine and induce poisoning. Capillary haemorrhage occurs in the dermis of fins and trunk and in the submucosa of the stomach. Hepatic cells and epithelia of renal tubules show degeneration. Glomeruli are destroyed and the tissue becomes haemorrhagic, with exudates of serum and fibrin (Miyazaki and Jo, 1985; Miyazaki and Kage, 1985).

Aeromonas species produce many products that may be toxic to other cells. Some are released from viable cells in soluble form. Others may remain associated with the cell surface, and still others may be released upon cell death. Three of the extracellular proteins of Aeromonas species—that have been implicated in pathogenicity—have been cloned, sequenced, and characterized biochemically. These are aerolysin, GCAT (glycerophospholipid:cholesterol acyltransferase), and a serine protease (Howard and Buckley, 1986; Buckley et al., 1991; Rodriguez et al, 1992)
Outbreaks of disease are usually associated with a change in environmental conditions. Stressors, including overcrowding, high temperature, a sudden change of temperature, rough handling, transfer of fish, low dissolved oxygen, poor nutritional status, and fungul or parasitic infection, contribute to physiological changes and heighten susceptibility to infection.

Control and Treatment
Prevention in Aquaculture (adpated from Warren, 1991)
1.Avoid hatchery to hatchery transfers of fish. Fish gradually develop resistance to local strains of bacteria but may carry virulent organisms to another hatchery when transferred.
2.Provide optimal environmental conditions for the species being reared, paying special attention to the maintenance of oxygen levels and the gentle handling of fish.
3.Prophylactic treatments are helpful when sorting, handling, or moving broodstock. Intraperitoneal injections of 10–30 mg per pound of body weight of aqueous chloramphenicol has reduced post-handling losses by 80–90 percent in Europe.
4.Antibiotics or disinfectants should be added to the water as a prophylactic measure when fish are transported in tank trucks or plastic bags. Acriflavin at 2–4 ppm has been used in routine fish transportation operations.

Therapy
Chemotherapeutic agents are used for the treatment of A. hydrophila in fish farms. Isolates of A. hydrophila in fish have been found to be sensitive to chloramphenicol, florfenicol, tetracycline, sulphonamide, nitrofuran derivatives, and pyrodinecarboxylic acids (Aoki and Egusa, 1971; Endo et al., 1973; Katae et al. 1979; Fukui et al. 1987). In hatchery operations, terramycin has been effective when incorporated into pelleted fish feed and fed at 3.5 grams of active drug per 100 pounds of fish per day for 10 days (Warren, 1991). [Note: Antibacterial therapy will provide only short-term relief if adverse environmental conditions such as high water temperatures, low water flows, low oxygen levels, or crowding are not promptly corrected].

The Disease (in Humans)
Bacteraemia (bacteria in the blood) is the most common pathogenic manifestation of Aeromonas in humans. Mild symptoms include fever and chills, but patients who become septic (overwhelming bacterial infection) with Aeromonas often exhibit abdominal pain, nausea, vomiting, and diarrhea.

Reports of Aeromonas wound infections have appeared increasingly in the literature. Unlike gastroenteritis, these infections can have fatal or serious debilitating outcomes, such as amputations. Aeromonas wounds fall into three categories, listed in order of increasing severity of damage caused: cellulitis, myonecrosis, and ecthyma gangrenosum.

Cellulitis, the most frequently encountered Aeromonas wound infection, is an acute inflammation of subcutaneous tissue characterized by redness and induration that may arise from injury or secondary to sepsis (Musher, 1980). Myonecrosis and ecthyma, the two less commonly seen types of Aeromonas infections, are typically found in patients that are immunocompromised. Myonecrosis, or bullous lesions, is characterized by the liquefaction of muscles with blackening of the tissue which may be gangrenous with gas formation. These patients require agressive antimicrobial therapy and debridement; those individuals that fail to respond to these measures may require amputation (Haburchak, 1996). The third type, ecthyma gangrenosum, is a cutaneous necrotic or gangrenous pustule that occurs secondary to sepsis. Lesions have an erythematous border surrounding a vesicle which can progress to necrosis of the soft tissue within 24 h. This type of infection is usually fatal (Musher, 1980).

Outcomes such as these serve as a sobering reminder to properly attend to wounds with clean water and antiseptics. Never wash a wound with lake or river water!
A. hydrophila infections require prompt attention at the first sign of onset. Most infections are treated with fluoroquinolones. Alternative agents include aztreonam, trimethoprim-sulfamethoxazole, third-generation cephalosporins, and/or aminoglycosides (Mani et al., 1995).

Reff From :
el_fahrybimantara.blogspot.com
John Hayes
MB592 - Diseases of Fish
Spring 2000 Term Project
Oregon State University