Anti-malaria property

Quinine Quinine, molecular formula C20H24N2O2, is a white crystalline quinoline alkaloid, isolated from Cinchona hark Cinchona succirubra), and is well known as an antimalarial drug. Quinine is extremely bitter, and also possesses antipyretic, analgesic and anti-inflammatory properties. While quinine is stiU the drug of choice for the treatment of Falciparum malaria, it can be also used to treat nocturnal leg cramps and arthritis. Quinine is an extremely basic compound, and is available in its salt forms, e.g. sulphate, hydrochloride and gluconate. 

Manzamines have shown a variety of bioactivities ineluding cytotoxicity, antimicrobial, pesticidal, and anti-inflammatory properties [2] some of them demonstrated effects on HTV and AIDS opportunistic infections [2], To date, the greatest potential for the manzamine alkaloids appears to be against malaria with manzamine A showing improved aetivity over the elinieally used drugs chloroquine and artemisinin both in vitro and in vivo [2]. 

This review has shown that many plants from Africa and other continents have been reported to be used to treat malaria in traditional medicine. Modem in vitro screens against the P. falciparum has confirmed the antimalarial properties for many of these plants and their extracts and clearly given the magnitude of the problem and the national costs due to malaria illness, death and suffering, the use of medicinal plants either in traditional manners and/or as leads for new compounds that may serve in the future for new anti-malarial drags presents scientific opportunities. 

In 1968, my graduate student Charles Walsh and I addressed the following question What are the pyrimidine sources for nucleic acid synthesis by Plasmodium lophurae We found the parasite synthesized pyrimidines de novo (Walsh and Sherman, 1968b). The evidence for a de novo synthesis was the presence of the key enzymes, thymidylate synthetase and oroti-dine-5-monophosphate pyrophosphorylase, as well as the demonstration of the incorporation of 14C-bicarbonate into cytosine, uracil and thymine. Finding a de novo pathway for the synthesis of pyrimidines by the malaria parasite would, in the next three decades, provide a biochemical basis for the mechanism of action of anti-folate anti-malarials as well as contributing to an understanding of the unique properties of the malaria parasite mitochondrion. 

Use Q. extracts are us in combination with other extracts in some antitussive and antiasthmatic preparations. The bark is used in traditional South American medicine for treatment of liver disorders, febrile colds, and for anti-allergic purposes it is recommended as a fever-lowering agent for malaria as well as an additive to phytopharmaceuticals with expectorant properties. Bark extracts are used industrially in South America to modify the tastes of alcoholic and non-alcoholic beverages, milk products, and for other food technological purposes. Cell suspension cultures started from shoots of the plants produce only few alkaloids, including the new alkaloid aspidochibine, with a novel skeletal type, 3-oxo-14,15-dehydrorha-zinilam, 11-hydroxytubotaiwine as well as a new dioxopiperazine... 

The large family of medicines known as nonsteroidal anti-inflammatory drags (NS AID, 3.3) today also owes its existence to primitive observations about the effect of the willow Salix in Latin). In this case, it was not the original compound, but a chemical derivative that became a blockbuster drag. The taste of willow bark is bitter, and similar to the taste of the bark of a South American plant Cinchona, which is an effective treatment against malaria. As well as the taste, the effect was also similar willow bark seemed to possess an antifever property. Today, it has been established that salicin is the active ingredient, but a simpler derivative named acetylsalicylic acid proved to be more potent (— 3.25), and is currently sold under the trade name Aspirin. 

To use a more sophisticated example, we can look to the products of the neem tree (Azadirzchta indica), a tropical plant that is known for its pesticidal properties. The seed of this tree is abundant with limonoids and simple terpenoids that are responsible for its biological activity. One particular limonoid found in the seed is Azadirachtin (2.134). The bioactivity of Azadirachtin potentially leads to a wide range of applications in herbal medicine and healthcare products for the treatment of malaria and tuberculosis and in anti-worm, clotting, and blood-detoxification preparations. These uses of Azadirachtin as a biopesticide or herbal medicine is limited due to solubility constraints in water and its instability as a result of its propensity to undergo complicated, irreversible rearrangements under acidic, basic and photolytic conditions. Consequently, there has been much research in the structural modification of Azadirachtin to overcome its solubility constraints to increase stability. This process normally involves many protection and deprotection synthetic steps and chromatographic separations. 

Febrifugine was first isolated from roots of Dichroa febrifuga Lour. (Saxifragaceae), a Chinese medicinal plant traditionally used to treat malaria fevers. This alkaloid showed potent anti-Plasmodium activity, which was superior to quinine, and tmacceptable side effects, such as hepatotoxicity and severe emesis [128,129]. Its properties not only precluded its use as drug but also encouraged the synthesis of safer analogues [127]. 

Substituted thieno[2,3-iflpyrimidines are considered to be an universal molecules in a structure-based drug design [119], Thieno[2,3-r pyrimidine derivatives show pronotmced anti-inflammatory [120], anti-tumor [121], radioprotective and anti-convulsing activity [122], The pharmacological versatility of the above system also present in substanees with depressant or sedative properties [123] and compoimds used for therapy of malaria [124], tuberculosis [125], Parkinson s disease [126] and other diseases were designed [127],... 

Rubiaceae, such as Cephaelis acuminata, Cephalis ipecacuanha, or Cephaelis accuminata. Ipecac alkaloids have powerful emetic and expectorant properties as well as anti-amoebic and antitumor activity, and some of them are widely used to treat amoebic dysentery (e.g., emetine and tubulosine), as well as schistosomiasis, leishmaniasis, and malaria (e.g., emetine). Isoquinoline alkaloid crispine A exhibits cytotoxic activity against SKOV3, KB, and HeLa human cancer lines and was isolated from C. crispus by Zhao et al. ... 

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