Laurent Dominique, Pietra Francesco
IRD (Institut de Recherche pour le Développement), UMR152 IRD-Université Paul Sabatier Toulouse III, Centre de Nouméa, BP A5, 98848, Nouméa, Nouvelle-Calédonie.
Mar Biotechnol (NY). 2006 Sep-Oct;8(5):433-47. doi: 10.1007/s10126-006-6100-y. Epub 2006 Mar 30.
The difficulty of obtaining an antimalarial vaccine along traditional lines, because of the highly adaptive character of the malaria parasite, prompts a ceaseless need for new drugs. To this end, marine organisms have been explored recently, as reviewed in this article within the perspective of clinically available antimalarial drugs and promising candidates. Most promising are tetrahydropyrrolo[1,2-alpha]pyrimidinium, bis-indole, and C(11)-N(5) alkaloids from sponges; pyridoacridone and decahydroquinoline alkaloids from ascidians; and pyrrole alkaloids from fungi, as well as polycyclic polyketides, norditerpene, and polyketide endoperoxides, terpene isonitriles, and, particularly, mixed-biogenesis alpha-galactosyl ceramides from sponges. The first and the latter classes of agents best fulfill the requirements for combinatorial synthesis in providing a wide variety of compounds for high-throughput screening and toxicity tests. These results came largely from nonprofit organizations, a trend that we foresee will continue. However, partnership with the pharmaceutical industry was and is needed to bring candidate drugs to the clinic. In any event, success will not be achieved without political plans to make the results of technology easily available to poor populations.
由于疟原虫具有高度适应性,按照传统方法研发抗疟疫苗存在困难,这就不断催生了对新药的需求。为此,本文从临床可用抗疟药物及有前景的候选药物的角度进行综述,探讨了近期对海洋生物的研究。最有前景的包括海绵中的四氢吡咯并[1,2-α]嘧啶鎓、双吲哚和C(11)-N(5)生物碱;海鞘中的吡啶吖啶酮和十氢喹啉生物碱;真菌中的吡咯生物碱,以及多环聚酮化合物、降二萜、聚酮内过氧化物、萜烯异腈,特别是海绵中的混合生源α-半乳糖神经酰胺。第一类和最后一类药物最符合组合合成的要求,能提供多种化合物用于高通量筛选和毒性测试。这些结果大多来自非营利组织,我们预计这一趋势将持续下去。然而,过去和现在都需要与制药行业合作,将候选药物推向临床。无论如何,如果没有使技术成果易于为贫困人口所用的政治计划,就无法取得成功。