A parasite is an organism living in or on, and metabolically depending on, another organism. Endoparasites live inside an organism, and ectoparasites live on the surface of the host. Parasites can be carnivorous if living with animals or herbivorous if living with plants. Analyses of parasite/host suggest strong evidence of anti-carnivorous anti-herbivorous action of alkaloids. A good example is with protozoan parasites (Plasmodium spp.) injected into humans by mosquitoes of the genus Anopheles. The life cycle of this parasite includes a sexual reproductive stage with multiplication (sporogony) occurring in the mosquito gut lumen and an asexual reproductive phase with multiplication (schizogony) occurring in the human host. Symptoms of this protozoan injection to humans and resulting symptoms of its asexual multiplication are known as malaria. Copp et al.393 have investigated the anti-parasitic potential of alkaloids against this kind of organism. In in vitro studies of anti-parasitic activity on Plasmodium falcicarum, Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei rhodesiense, evidence arose that connected pyridoacridone alkaloids with anti-parasitism. However, these alkaloids also exhibit high cytotoxic activity, which can limit the use of their bioactivity in possible anti-malarial product development. Kapil443 has studied the bioactivity of piperine on L. donovani promastigotes in vitro and received very promising results. According to this study, piperine exhibited a concentration-dependent inhibition of L. donovani promastigotes.
More recently Wright444 has analysed bioactive possibilities of cryptoleptine, the main alkaloid from Cryptolepis sanguinolenta, as an anti-malarial agent. The bioactivity of alkaloids against parasites is becoming increasingly important because some parasites (e.g. P. falciparum) are presently resistant to traditional malarial medication. Cryptoleptine was considered by Wright444 as an alkaloid having possibility to be an anti-malarial bioagent. However, more research in this direction is very important. As is known, the first alkaloid to be used against malaria was quinine obtained from the bark of Cinchona. Treatment was later commonly focused on quinoline-based drugs such as chloro-quine, quinine, mefloquine, primaquine and fansidar. Observations that P. falciparum became resistant to chloroquine, mefloquine and halofartine445,446 aroused awareness of a problem. This has been studied in connection to indole alkaloids (Figure 86) from the Strychnos species (Loganiaceae) by Frederich et al.447 Sun-gucine presented very little activity, but some compounds (strychnogucine B and 18-hydroxyisosungucine) displayed more active qualities against quinine- and chloroquinine-resistant strains of P. falciparum. Anti-parasitic alkaloid activity against Leishmania spp. has also been reported in other studies448,449,450,451. Montenegro et al.451 have studied alkaloids (xylopine, nornanteine, cryptodorine, nornuciferine, lysicamine and laudanosine) from Guatteria amplifolia Triana and Planch (Annonaceae). Their results provide evidence that xylopine, cryptodorine, nornanteine and nornuciferine have significant bioactive properties against Leish-mania mexicana and Leishmania panamensis. Xylopine was the most active compound451. Moreover, Sari et al.452 have studied the bioactivity of alkaloids from Papaver lateritium Koch, a plant endemic to Turkey. The quaternary alkaloid fraction with (—)-mecambridine showed the highest lethality to brine shrimp larvae. Moreover, a study of the bioactivity of Stemona alkaloids provides evidence that these alkaloids have anti-tussive activity330. This study also demonstrates a clear structure-bioactivity relationship in such alkaloids. Through substitution of a constituent of the alkaloid ring structure, it is possible to change bioactivity.
Many alkaloids are toxic to foreign organisms. Toxicity is a secondary function of the alkaloids, because they are generally non-toxic to the organisms producing them. This is very important for understanding alkaloid nature. There are many studies on alkaloid toxins published in recent years453'454'455'456'457'458'459'460. The biotoxicity of alkaloids is selective and dependent on different organisms and the chemical structure of alkaloids themselves. Multiple bonds and different bond groups and sub-groups especially directly or indirectly influence toxicity mechanisms.
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