Anticancer metal compounds in NCI's tumor-screening database: putative mode of action

Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action

“…We have previously established the general MOA of the agents in some of these SOM regions: mitosis (M), membrane function and oxidative stress (N), nucleic acid metabolism (S), and metabolic stress and cell survival (Q), oxidative metabolism (R), and kinases/phosphatases and oxidative stress (P), via other methods. 16,23,24 The pathway mapping results provide additional support for the annotation of some of the SOM regions: for example, the GO terms mitotic checkpoint, cytokinesis, kinetochore, and cell cycle are associated with the M-region; the GO terms mitochondrial inner membrane (data not shown), response to oxidative stress (data not shown), and oxidoreductase activity are associated with the N-region; the KEGG pathway one carbon pool by folate, the BioCarta granzyme Amediated apoptosis pathway, the GO terms DNA topological change and DNA topoisomerase (ATP-hydrolyzing) activity, are associated with the S-region; the KEGG pathway glutamate metabolism and the GO terms (data not shown) xenobiotic metabolism, cysteine metabolism, and glutathione biosynthesis are associated with the Q-region; the KEGG pathways fatty acid metabolism and oxidative For each pathway, the table lists the name of the pathway, the significance level of the connection between the pathway and its small-molecule inhibitors (P-value), and the number of references where the small molecule is documented as an inhibitor of the product of a gene in the pathway (see Supplementary Information, Table IV, Galactose metabolism N hsa00252…”

“…21 GI 50 growth patterns have been found to be an informationrich resource for establishing a compound's MOA. 16,[22][23][24] SOM clustering of the GI 50 data segregates compounds into nine major response categories: mitosis (M), membrane function (N), nucleic acid metabolism (S), metabolic stress and cell survival (Q), kinases/phosphatases and oxidative stress (P), and four unexplored regions R, F, J, and V. 16,23,24 Each of these regions is further divided into a total of 80 clades (a clade is a group of clusters (nodes) that share similar cytotoxic responses) (subregions: M 1 -M 8 , N 1 -N 13 , P 1 -P 8 , Q 1 -Q 7 , R 1 -R 7 , S 1 -S 13 , F 1 -F 8 , J 1 -J 8 , V 1 -V 8 ) (Figure 1). The current SOM extends our previously published analysis to include the existing complement of newly screened compounds.…”

Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2′-hydroxyphenyl)benzoxazole analogs of UK-1

“…However, the exact role of metal ion coordination in the mechanism of action of UK-1 and analogs remains to be determined. There is a growing interest in the role of metal ions and their complexes in drug design [11][12][13][14], particularly in metal complex-DNA interactions [15][16][17][18][19][20][21]. Studies of UK-1 and its analogs may offer important insights, provided by nature, into how metal ion complexation can be harnessed in the design of selective cytotoxins.…”

Cytotoxic effect of palladium (II) inclusion compounds in beta-cyclodextrin

“…En este contexto, se han presentado como promisorios aquellos que recurren a compuestos de metales pesados (rodio, paladio, plata, iridio platino, oro, mercurio, estaño, plomo, antimonio y bismuto, entre otros) y de ligandos de las tiosemicarbazonas. Los resultados del perfil citotóxico indican que tienen especificidad frente a ciertas células tumorales, según sus propiedades (27).…”