Project of Research - PNCDI 2 PC 2007
Details: CMNP-1712/2007
Contract no. 61-037 / 14.09.2007

DEVELOPMENT OF A BIOINFORMATIC QSAR SYSTEM FOR ANTITUMORAL AND ANTIRHEUMATIC DRUG SUBSTANCES MODELLING IN INDIVIDUALIZED THERAPIES

Tematical Aria : Biotechnology
Director : Assoc. Prof. POPA LACRAMIOARA, PhD., Pharm.

The project purpose is related to obtaining robust QSAR/QSPR predictive models for antitumoral activity and antirheumatic/antitumoral activity, in a specialized bioinformatic framework, designed, developed and validated for this purpose.

In the development of the project it is envisaged elaboration of a new QSAR software, which allows molecular-structural description throughout quantical descriptors for the conventional drug substances used as antitumoral agents, for the anti-inflammatory agents with antitumoral component activity (Cytostatic DMARDs), as for the any class of therapeutic agents. The QSAR analysis will permit delivering robust models for prediction and discriminate therapeutic related activity (expressed at cellular level modifications), correlated with quantical molecular description.

The in silico results will be further evaluated in vitro, in cellular model using standard antitumoral agents as well as standard anti-rheumatic agents with antitumoral correlated activity. The in vitro cellular test results will be further correlated with the in vitro interference of the mentioned drug substances and with relevant enzymatic substrate. The algorithm will be repeated for each of the selected class of agents apart and finally for these ones in individualized therapies.

In a final phase, the bioinformatic platform created and validated will be applied to reach the best QSAR models for prediction/discriminate antitumoral and anti-inflammatory/antitumoral activity in individualized therapies. The predictive results will be preloaded and verified in experimental in individual variability in vitro cellular assays for the antitumoral standard agents, and of the individual effect of these standard antitumoral/antirheumatic agents upon enzymatic support. The bioinformatic system created through project development are initiated with the software as specialized application for corelations quantic chemical structure biologic/pharmacologic activity; experimentation of this software for the antitumoral/antirheumatic therapy, the permanent adaptation through feed-back signals from all activities and phases in the work plan flow of the project. The bioinformatic platform could be take over and apllied for any therapeutic agents, and the results of the in silico computer modelling will contribute to the creation of a QSAR models Digital Library.

It is proposed the development of a modern approach in cancer therapy, especially in individualized therapies, guided to molecular, chemical support, for knowledge discovery and optimization of molecular targets and of the responsible factors for variability of biologic response.