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PLANTS AND ARSENICALS AS THERAPEUTIC AGENTS
 

PLANTS AND ARSENICALS AS THERAPEUTIC AGENTS

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Use of Plants and Arsenicals as therapeutic agents.

Use of Plants and Arsenicals as therapeutic agents.

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    PLANTS AND ARSENICALS AS THERAPEUTIC AGENTS PLANTS AND ARSENICALS AS THERAPEUTIC AGENTS Presentation Transcript

    • PLANTS AND ARSENICALS AS THERAPEUTIC AGENTS. MAJID MOHIUDDIN
      • Historically, plants have provided a good soure of antiinfective agents: emetine, quinine and berberine.
      • Phytomedicines.
      • Protoberberines and related alkaloids, picralima-type indole alkaloids and garcinia biflavonones.
      • Hydrastis canadensis (goldenseal)
      • Garcinia kola (bitter kola)
      • Polygonum sp.,Aframonum melegueta (grains of paradise)
      • New drugs such as Xylopia aethiopica, Araliopsis tabouensis, Cryptolepis sanuinolenta, Chasmanthera dependens and Nauclea.
      • HISTORIC USE OF PLANTS AS ANTIMICROBIALS:
      • Base for the development of a medicine, new drugs.
      • Phytomedicine to be used for the treatment of disease.
      • Classified as antiinfective:
      • The isoquinoline alkaloid emetine obtained from the underground part of Cephaelis ipecacuanha – amoebicidal drug – for abscesses ( Escherichia histolytica) .
      • Quinine since 1630’s – alkaloid of bark of Chinchona tree – for malaria and nocturnal leg cramps.
      • Analogs quinine drugs such as chloroquine.
      • Higher plants – antileukaemic alkaloids, vinblatine and vincristine – from Madagascan periwinkle ( Catharanthus roseus syn. Vinca roseus) .
      • Other cancer therapeutic agent include taxol, homoharringtonine and several derivatives of camptothecin. Eg., Benzylisoquinoline alkaloid, papaverine – effect on cytomegalovirus, measles and HIV.
    • PLANTS WITH PROMISING ANTIINFECTIVE ACTIVITY
      • Garcinia kola, bitter kola (Guittiferae)
      • Moist forest
      • up to 12 m high.West and Central Africa.
      • Medicinally – purgative, antiprasitic,
      • antimicrobial.
      • Seeds – for bronchitis and throat infections.
      • Prevent and relieve colic, cure head or
      • chest colds and relieve cough.
      • Liver disorders and as a chewing stick.
      • Biflavonoids, xanthones and benzophenones.
      • Antimicrobial properties – benzophenone, favanones.
      • Anti-inflammatory, antimicrobial and antiviral properties.
      • Possesses antidiabetic and antihepatotoxic activities.
      • Aframomum melegueta (Zingiberaceae) Grains of Paradise.
      • Tropics
      • Spicy edible fruit
      • Perennial herb
      • Aphrodisiac, measles and leprosy, hemorrhage, purgative, galactogogue and anthelmintic and hemostatic agent.
      • Essential oils – gingerol, shagaol, paradol.
      • Antimicrobial and antifungal activity.
    • Aframomum melegueta (Zingiberaceae) Grains of Paradise.
      • Xylopia aethiopica, Ethiopian Pepper (Abbibacceae)
      • Evergreen, aromatic tree – 20m high with peppery fruit.
      • Lowland rainforest and moist fringe – savanna zones of in Africa.
      • As a cough remedy and as a post partum tonic and lactation aid.
      • Stomachache, bronchitis, biliousness and dysentery.
      • Headache and neuralgia.
      • Lemon grass for female hygiene.
      • High in copper, manganese and zinc.
      • Constituents – diterpenic and xylopic acid.
      • For Gram +ve and – ve bacteria.
      • Effective against E.coli.
      • Xylopic acid – activity against Candida albicans.
    • Xylopia aethiopica, Ethiopian Pepper (Abbibacceae)
      • Cryptolepis sanguinolenta Lindl.Schltr. (Periplocaceae)
      • Rainforest and deciduous belt forest, found in the west coast of Africa.
      • Fever , Urinary tract infections, especially Candida.
      • Inflammatory conditions, malaria, hypertension, microbial infections and inflammatory conditions, stomach aches colic.
      • Indo quinoline alkaloids.
      • Inhibition against gram negative bacteria and yeast.
      • Bactericidal activity.
      • Extracts is effective in parasitemia.
      • Bacteria specifically, enteric pathogens, most notably E.coli ( but also staphylococcus, S.coli, C.jejuni, pseudomonous, salmonella, shigella, streptococcua and vibrio) and some activity against candida.
      • Shows histamine antagonism, hypotensive and vasodilatory activities.
      • Antihyperglycyemia properties
      • Chasmanthera dependen Hoschst (Menispermaceae)
      • Woody climber
      • Forest margins.
      • Venereal disease –topically on sprained joints and bruises and as a general tonic for physical and nervous debilities.
      • Berberine type alkaloids, palmatine, colombamine and jateorhizine.
      • Plant inhibits lieshmania.
      • Nauclea latifolia Smith (Rubiaceae)
      • Forest and fringe tropical forest.
      • Tonic and fever medicine, chewing stick, toothaches, dental caries, septic mouth and malaria, diarrhea and dysentery.
      • Indole-quinolizidine alkaloids and glycoalkaloids and sapponins.
      • Root – Gram +ve and –ve and antifungal activity.
      • Corynebacterium diphtheria, streptobacillis sp., Streptococcus sp., Neisseria sp., Pseudomonas aeruginosa, Salmonella sp.
    • Nauclea latifolia Smith (Rubiaceae)
      • Araliopsis tabouensis (Rutaceae)
      • Treatment of sexually transmitted diseases.
      • The bark infusion is drunk for gonorrhea.Alkaloids – 7 alkaloids root and stem bark.
    • Arsenicals
      • Paul Ehrlich used organoarsenic (“arsenicals”) for the treatment of syphilis, demonstrating the relevance of metals, or at least metalloids, to medicine, that blossomed with Rosenberg’s discovery of the anti-cancer activity of cisplatin (cis-PtCl2(NH3)2).
      • Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon.
      • A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungicides.
      • In general these applications are declining in step with growing concerns about their impact on the environment and human health. The parent compound is arsine. Despite their toxicity, organoarsenic biomolecules are well known.
      • Bioinorganics
      • During the 18th, 19th, and 20th centuries, arsphenamine (by Paul Ehrlich) and arsenic trioxide (by Thomas Fowler).
      • Arsphenamine as well as Neosalvarsan was indicated for syphilis and trypanosomiasis, but has been superseded by modern antibiotics.
      • It was the first important antisyphillitic, though was phased out in the 1930s by better arsenical compounds ( neoarsphenamine ), and eventually altogether by penicillin.
      • Arsenic trioxide has been used in a variety of ways over the past 200 years, but most commonly in the treatment of cancer . The US Food and Drug Administration in 2000 approved this compound for the treatment of patients with acute promyelocytic leukemia that is resistant to ATRA ( all-trans retinoic acid) . It was also used as Fowler's solution in psoriasis.
      • Recently new research has been done in locating tumours using arsenic-74 (a positron emitter). The advantages of using this isotope instead of the previously used iodine-124 is that the signal in the PET scan is clearer as the iodine tends to transport iodine to the thyroid gland producing a lot of noise.
      • Arsanilic acid is the organoarsenic compound also called p -aminophenylarsenic acid. This colourless solid was used as a drug in the late 19th and early 20th centuries but is now considered prohibitively toxic. Arsanilic acid is a derivative of phenylarsonic acid with an amine in the 4-position.
      • Arsanilic acid was first reported in 1859 by Antoine Béchamp. Béchamp optimistically chose the name Atoxyl , referring to its reduced toxicity compared to arsenic. The original synthesis, which involved the reaction of aniline and arsenic acid, remains useful today.
        • C6H5NH2 + H3AsO4 -> H2O3AsC6H4NH2 + H2O
      • Arsanilic acid was initially used in medicine to treat simple skin diseases. In 1905, two British physicians, H.W. Thomas and A. Breinl, reported that Atoxyl was active against the trypanosomes of sleeping sickness.
      • The effect was however not very pronounced and the necessary dosage was so high that toxic side effects far outweighed the benefits. It frequently caused blindness by damaging the optic nerve and other varied disorders.
      • Nevertheless, the discovery of arsanilic acid's activity against trypanosomes was the basis for a major advance by the bacteriologist Paul Ehrlich. Ehrlich, who believed that the formula was incorrect, and the organic chemist Alfred Bertheim revised the structural assignment. The correct formula suggested new ways that the atoxyl molecule could be modified, and a series of such derivatives were then synthesized. Testing for anti-syphilitic activity was performed by Sahachiro Hata who worked in Ehrlich's lab. The result of this collaboration was the discovery of the drug Salvarsan in 1909, which also was later abandoned but which accelerated the growth of medicinal chemistry.
      • Although the practice is controversial, arsanilic acid and related compounds are sometimes used in treating dysentery in swine.
    • MAJID MOHIUDDIN THANK YOU