We give here a nice example to analyse antibiotic leads compounds. The examples are Isoquinolines explained in the following article:
"Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells"
Alexander Cecil, Carina Rikanović, Knut Ohlsen, Chunguang Liang, Jörg Bernhardt, Tobias A Oelschlaeger,
Tanja Gulder, Gerhard Bringmann, Ulrike Holzgrabe, Matthias Unger and Thomas Dandekar
Isoquinolines (IQs) are natural substances with an antibiotic potential we want to compare to optimize their action. Specifically, IQ-238 is a synthetic analog of the novel-type N,C-coupled naphtylisoquinoline (NIQ) alkaloid ancisheynine. Similar novel synthetic substances include IQ-143 and further NIQs. By utilizing gene expression data for metabolic network modeling and voronoi tessalation as well as cytotoxity measurements and chemical properties of the NIQs for a principal component analysis, we could show that IQ-238 has strong antibiotic potential for staphylococci and low cytotoxicity against human cells. Systemic effects are less than for IQ-143 and only involve carbohydrate metabolism allowing for a good therapeutic window. Our combination of analysis methods allows suggestions for further lead development regarding specific chemical modification and substitutions for the naphtyl moiety in NIQs.
Contained in this file are the R-scripts used to compute the results of the publication. Also contained is a tutorial with step-by-step instructions for the software package YANAsquare as well as the R-scripts mentioned above.