High-Throughput Analysis of the Drug Mode of Action of PB28, MC18 and MC70, Three Cyclohexylpiperazine Derivative New Molecules

Authors:
Vitoantonio Bevilacqua;Paolo Pannarale;Giuseppe Mastronardi;Amalia Azzariti;Stefania Tommasi;Filippo Menolascina;Francesco Iorio;Diego Bernardo;Angelo Paradiso;Nicola A. Colabufo;Francesco Berardi;Roberto Perrone;Roberto Tagliaferri
Affiliations:
Dipartimento di Elettrotecnica ed Elettronica, Polytechnic of Bari, Bari, Italy 70125;Dipartimento di Elettrotecnica ed Elettronica, Polytechnic of Bari, Bari, Italy 70125;Dipartimento di Elettrotecnica ed Elettronica, Polytechnic of Bari, Bari, Italy 70125;IRCCS Ospedale Oncologico di Bari, , Bari, Italy 10 70126;IRCCS Ospedale Oncologico di Bari, , Bari, Italy 10 70126;Dipartimento di Elettrotecnica ed Elettronica, Polytechnic of Bari, Bari, Italy 70125;TIGEM - TeleThon Institute of Genetics and Medicine, , Napoly, Italy 111 80131 and Department of Mathematics and Informatics, University of Salerno, Fisciano (SA), Italy 84084;TIGEM - TeleThon Institute of Genetics and Medicine, , Napoly, Italy 111 80131;IRCCS Ospedale Oncologico di Bari, , Bari, Italy 10 70126;Department Farmaco Chimico, University of Bari, Bari, Italy 70125;Department Farmaco Chimico, University of Bari, Bari, Italy 70125;Department Farmaco Chimico, University of Bari, Bari, Italy 70125;Department of Mathematics and Informatics, University of Salerno, Fisciano (SA), Italy 84084
Venue:
ICIC '08 Proceedings of the 4th international conference on Intelligent Computing: Advanced Intelligent Computing Theories and Applications - with Aspects of Artificial Intelligence
Year:
2008

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Abstract

Objective: This work explores the mode of action of PB28, MC70 and MC18 three molecules that showed anti-tumoral properties by arresting cellular growth and inhibiting glycoprotein P. Methods: Here we conduct a microarray-based study and analyze the expression patterns associated with the action of drugs. An ontology based analysis has been conducted, and the individuated cellular processes have been analyzed with gene networks, examining the interactions among genes. A clustering analysis revealed mechanisms shared with other drugs. Results: The results indicate that this compounds have side effects that include inflammatory response and fever, induced by the interleukin signaling pathway. Other evidences related with known effects of the compounds were highlighted. Conclusions: The results indicate that the direct effects could be reached at a post-transcriptional level of P-gp or through other targets, further studies will address these hypothesis. The prediction of side effects will be useful in subsequent in vivoexperiments.