ABSTRACT
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 GI50 values of 1.40 µM and 1.52 µM, whereas the GI50 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.
Subject(s)
Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Quantitative Structure-Activity Relationship , Thiocarbamates/pharmacology , A549 Cells , Anthraquinones/chemistry , Cell Survival/drug effects , Drug Screening Assays, Antitumor , HT29 Cells , Humans , MCF-7 Cells , Rhodamines/chemistry , Software , Thiocarbamates/chemistry , Tumor Cells, CulturedABSTRACT
The influence of new derivatives of 9,10-anthraquinone with benzoylthiourea, thiazole, triazole and amino acid fragments on the activity of membrane-associated tyrosine kinases was investigated. Inhibitors of protein tyrosine kinase activity of the membrane fraction, as promising agents to search for new potential anticancer agents among the studied compounds, were discovered.
