Stasevych M, Zvarych V, Lunin V, Deniz N G, Gokmen Z, Akgun O, Ulukaya E, Poroikov V, Gloriozova T, Novikov V
a Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology , Lviv Polytechnic National University , Lviv , Ukraine.
b Department of Chemistry , Istanbul University , Istanbul , Turkey.
SAR QSAR Environ Res. 2017 May;28(5):355-366. doi: 10.1080/1062936X.2017.1323796. Epub 2017 May 19.
Anticancer activity as an associated action for a series of dithiocarbamates of 9,10-anthracenedione was predicted using the PASS computer program and analysed with PharmaExpert software. The predicted cytotoxic activity of the dithiocarbamate derivatives of 9,10-anthracenedione was evaluated in vitro on cancer cells of the human lung (A549), prostate (PC3), colon (HT29) and human breast (MCF7) using the sulforhodamine B (SRB) cell viability assay. Among these compounds, 9,10-dioxo-9,10-dihydroanthracen-1-yl pyrrolidin-1-carbodithioate and 9,10-dioxo-9,10-dihydroanthracen-2-yl pyrrolidin-1-carbodithioate were identified as the most potent anticancer agents with cytotoxic activity against the MCF-7 human breast cell line with GI values of 1.40 μM and 1.52 μM, whereas the GI value for the reference anticancer drug mitoxantrone was 3.93 μM. Thus, anticancer activity predicted by PASS with a probability Pa > 30% was confirmed by the experiment. Relatively small Pa values estimated by PASS indicated the novelty of the considered derivatives comparing to the compounds from the PASS training set.
使用PASS计算机程序预测了一系列9,10-蒽二酮二硫代氨基甲酸盐的抗癌活性，并使用PharmaExpert软件进行分析。采用磺酰罗丹明B（SRB）细胞活力测定法，在体外评估了9,10-蒽二酮二硫代氨基甲酸盐衍生物对人肺癌（A549）、前列腺癌（PC3）、结肠癌（HT29）和人乳腺癌（MCF7）细胞的预测细胞毒性活性。在这些化合物中，9,10-二氧代-9,10-二氢蒽-1-基吡咯烷-1-碳二硫代酸盐和9,10-二氧代-9,10-二氢蒽-2-基吡咯烷-1-碳二硫代酸盐被确定为最有效的抗癌剂，对MCF-7人乳腺癌细胞系具有细胞毒性活性，GI值分别为1.40 μM和1.52 μM，而参考抗癌药物米托蒽醌的GI值为3.93 μM。因此，PASS预测的概率Pa>30%的抗癌活性得到了实验证实。PASS估计的相对较小的Pa值表明，与PASS训练集中的化合物相比，所考虑的衍生物具有新颖性。
