Pinto A V, Pinto C N, Pinto M do C, Rita R S, Pezzella C A, de Castro S L
Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
Arzneimittelforschung. 1997 Jan;47(1):74-9.
Continuing a program on the chemistry and biological activity of compounds from the Brazilian flora, the lytic activity against bloodstream forms of T. cruzi of nine new heterocyclic naphthooxazole and naphthoimidazole derivatives obtained from the reaction of naphtoquinones isolated from Tabebuia sp. (Tecoma) with amino-containing reagents has been studied. Also for the first time the biological activity of allyl derivatives of lawsone, a natural quinone from Lausonia alba inactive against T. cruzi, is reported. The introduction of an allyl group in lawsone gives rise to O-allyl-lawsone and C-allyl-lawsone that showed activity against the parasite, with ID50 values of 420.7 +/- 71.1 and 330.7 +/- 62.4 mumol/l, respectively. The trypanocidal activity of the naphtho heterocyclics synthesized from the original quinones showed no concordant behavior in relation to the parent compound. Six of nine of the synthesized compounds presented lower ID50 values than crystal violet, indicating a general trend of activity among naphthalenic heterocyclics of the oxazole/imidazole type. However, their chemical structures do not endow them with the capacity of free radical generation by biological reduction as the quinoidal moiety, nor do they have chemical reducible appendage like the nitro group of nifurtimox and benznidazole, responsible for such behaviour. As a hypothesis, the pattern of their biological actions should be focused in other aspects of their chemical structures. Because of their polycyclic planar topology, these derivatives are potential candidates for experimental tests as DNA intercalating agents.
继续开展关于巴西植物区系化合物的化学和生物活性的项目，我们研究了从Tabebuia sp.（紫薇科）中分离出的萘醌与含氨基试剂反应得到的9种新型杂环萘并恶唑和萘并咪唑衍生物对克氏锥虫血流型的裂解活性。此外，首次报道了来自白木香的天然醌拉索酸对克氏锥虫无活性的烯丙基衍生物的生物活性。在拉索酸中引入烯丙基可得到O - 烯丙基 - 拉索酸和C - 烯丙基 - 拉索酸，它们对该寄生虫具有活性，ID50值分别为420.7±71.1和330.7±62.4μmol/L。由原始醌合成的萘并杂环化合物的杀锥虫活性与母体化合物相比没有一致的行为。9种合成化合物中有6种的ID50值低于结晶紫，表明恶唑/咪唑型萘并杂环化合物具有普遍的活性趋势。然而，它们的化学结构并未赋予它们像醌类部分那样通过生物还原产生自由基的能力，也没有像硝呋替莫和苯硝唑的硝基那样具有可化学还原的基团来负责这种行为。作为一种假设，它们的生物作用模式应聚焦于其化学结构的其他方面。由于它们的多环平面拓扑结构，这些衍生物是作为DNA嵌入剂进行实验测试的潜在候选物。
