Chemical and Bioactivity Information Centre, Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon,
J Mol Model. 2014 Jan;20(1):2069. doi: 10.1007/s00894-014-2069-z. Epub 2014 Jan 24.
We attempt to evaluate the "drug-likeness" of a collection of ∼1500 natural products, exhibiting in vitro or in vivo activities against cancers of various forms, by using a set of calculated molecular descriptors. Compliance to Lipinski's "Rule of Five" and Jorgensen's "Rule of Three" have been used to assess oral availability, by making use of popular parameters like molecular weights, predicted lipophilicities, number of hydrogen bond donors/acceptors, predicted aqueous solubilities, number of primary metabolites and Caco-2 permeabilities. Meanwhile 24 descriptors have been used to predict properties related to the absorption, distribution, metabolism, elimination, and toxicity (ADMET). The ADMET profiles of the anticancer natural products have been analyzed in comparision with the range of properties for 95 % of known drugs. Our results show that the computed parameters fall within the recommended range for about 42 % of the studied compounds, while respectively 63 % and 69 % of the corresponding 'drug-like' and 'lead-like' subsets had properties predicted to fall within the recommended range for 95 % of known drugs. The aim of giving a picture of how drug-like they are and bring out the need to return to natural sources in searching for anticancer lead compounds.
我们试图通过一组计算得到的分子描述符来评估约 1500 种具有各种形式抗癌活性的天然产物的“类药性”。通过使用分子重量、预测脂溶性、氢键供体/受体数量、预测水溶性、初级代谢物数量和 Caco-2 渗透率等流行参数，我们遵守了 Lipinski 的“五规则”和 Jorgensen 的“三规则”，以评估口服可用性。同时，我们使用了 24 个描述符来预测与吸收、分布、代谢、排泄和毒性 (ADMET) 相关的性质。我们分析了抗癌天然产物的 ADMET 谱，并与已知药物的 95%的性质范围进行了比较。我们的结果表明，计算得到的参数大约有 42%落在推荐范围内，而相应的“类药性”和“先导化合物性”子集分别有 63%和 69%的化合物预测性质落在已知药物的 95%推荐范围内。目的是给出它们的类药性的大致图像，并说明需要从天然来源中寻找抗癌先导化合物。
