El-Elimat Tamam, Zhang Xiaoli, Jarjoura David, Moy Franklin J, Orjala Jimmy, Kinghorn A Douglas, Pearce Cedric J, Oberlies Nicholas H
Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, P.O. Box 26170, Greensboro, NC 27402.
ACS Med Chem Lett. 2012 Jul 12;3(8):645-649. doi: 10.1021/ml300105s.
A collaborative project has been undertaken to explore filamentous fungi, cyanobacteria, and tropical plants for anti-cancer drug leads. Through principal component analysis, the chemical space covered by compounds isolated and characterized from these three sources over the last four years was compared to each other and to the chemical space of selected FDA-approved anticancer drugs. Using literature precedence, nine molecular descriptors were examined: molecular weight, number of chiral centers, number of rotatable bonds, number of acceptor atoms for H-bonds (N,O,F), number of donor atoms for H-bonds (N and O), topological polar surface area using N,O polar contributions, Moriguchi octanol-water partition coefficient, number of nitrogen atoms, and number of oxygen atoms. Four principal components explained 87% of the variation found among 343 bioactive natural products and 96 FDA-approved anticancer drugs. Across the four dimensions, fungal, cyanobacterial and plant isolates occupied both similar and distinct areas of chemical space that collectively aligned well with FDA-approved anticancer agents. Thus, examining three separate re-sources for anticancer drug leads yields compounds that probe chemical space in a complementary fashion.
一个合作项目已开展，旨在探索丝状真菌、蓝细菌和热带植物以寻找抗癌药物先导物。通过主成分分析，将过去四年从这三种来源分离和表征的化合物所覆盖的化学空间相互比较，并与选定的FDA批准的抗癌药物的化学空间进行比较。利用文献先例，研究了九个分子描述符：分子量、手性中心数量、可旋转键数量、氢键受体原子数量（N、O、F）、氢键供体原子数量（N和O）、使用N、O极性贡献的拓扑极性表面积、森口正醇 - 水分配系数、氮原子数量和氧原子数量。四个主成分解释了343种生物活性天然产物和96种FDA批准的抗癌药物之间87%的变异。在这四个维度上，真菌、蓝细菌和植物分离物占据了化学空间中既相似又不同的区域，这些区域与FDA批准的抗癌药物总体上排列良好。因此，研究三种不同的抗癌药物先导物来源会产生以互补方式探索化学空间的化合物。
