In silico-driven identification of novel molluscicides effective against Biomphalaria glabrata (Say, 1818),New Journal of Chemistry

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In silico-driven identification of novel molluscicides effective against Biomphalaria glabrata (Say, 1818)
New Journal of Chemistry ( IF 2.7 ) Pub Date : 2020-09-25 , DOI: 10.1039/d0nj03314f
Daniela Braz dos Santos _{1,

2,

3,

4,

5} , José Teófilo Moreira-Filho _{1,

2,

3,

4,

5} , Amanda de Oliveira Melo _{5,

6,

7,

8} , Josiel Araújo Lemes _{5,

6,

7,

8} , Luciana Damacena Silva _{5,

8,

9,

10} , Thiago Lopes Rocha _{2,

3,

4,

5,

11} , Carolina Horta Andrade _{3,

4,

5,

12,

13} , Bruno Junior Neves _{3,

4,

5,

12,

13} , José Clecildo Barreto Bezerra _{1,

2,

3,

4,

5}

Affiliation

Schistosomiasis control in endemic areas depends on several factors, including mass drug delivery programs and interrupting the transmission of disease by controlling the intermediate host snails in the freshwater ecosystem using molluscicides. However, the use of the gold standard molluscicide, i.e., niclosamide, has been considered problematic due to its high cost, toxicity for aquatic organisms, and the emergence of niclosamide-resistant snail populations. In this work, we report the in silico driven identification of novel naphthoquinone compounds with high molluscicidal activity against Biomphalaria glabrata. For this purpose, we developed statistically robust and validated shape-based and machine learning models using B. glabrata bioassay compounds data. Using these models, we prioritized fourteen naphthoquinone compounds for further in vivo testing against adult, newly-hatched, and embryo of B. glabrata snails. Among them, compounds 3, 5, 6, 7, and 12 were the best candidates, presenting moderate potency against adult snails (LC₅₀: 28.98–102.24 μM) and high potency (LC₅₀: 14.52–0.45 μM) against newly-hatched snails and embryos. To summarize, the in silico approach explored here allowed us to discover five new molluscicidal candidates for prospective field studies.

中文翻译：

在计算机上驱动的新型抗软体动物杀虫剂的鉴定，该杀虫剂有效地对抗了光滑小球藻（Say，1818）

流行地区的血吸虫病控制取决于几个因素，包括大规模药物输送计划和通过使用杀灭杀虫剂控制淡水生态系统中的中间宿主蜗牛来中断疾病的传播。然而，由于金标准杀软体动物剂，即烟酰胺，由于其高成本，对水生生物的毒性以及耐烟酰胺的蜗牛种群的出现而被认为是有问题的。在这项工作中，我们报告了在计算机上驱动的新型萘酚化合物的鉴定，这些化合物具有高杀虫活性，可对光滑小生辉菌（Biomphalaria glabrata）起作用。为此，我们使用了光滑双歧杆菌（B. glabrata）开发了经过统计验证且经过验证的基于形状的机器学习模型生物测定化合物数据。使用这些模型，我们确定了14种萘醌化合物的优先级，以进一步针对glabrata蜗牛的成年，新孵化和胚胎进行体内测试。其中，化合物3，5，6，7，和12是最好的候选者，呈现针对成人中度蜗牛效力（LC ₅₀：28.98-102.24μM）和高效力（LC ₅₀：14.52-0.45μM）针对新孵化蜗牛和胚胎。总而言之，这里探讨的计算机方法使我们能够发现五种新的杀软体动物候选物，用于前瞻性田野研究。

更新日期：2020-10-15

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