Influence of structural factors in the modulation of cytotoxic activity

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Leonor C�?´rte-Real1, M Paula Robalo1, 2, Fernanda Marques1, Guilherme Nogueira1, A Isabel Tomaz1, M Helena Garcia1 and Andreia Valente1

1Universidade de Lisboa, Portugal 2Instituto Superior de Engenharia de Lisboa, Portugal

Posters-Accepted Abstracts: Med chem

Abstract :

The development of new drugs to fight cancer is of upmost importance since this disease is responsible for millions of deaths each year. The drugs in clinical use, mainly based on platinum, only treat a limited range of cancers and own a lack of selectivity towards malignant cells, resulting in serious side effects. Ruthenium is a promising alternative due its unique chemistry. Two very well-known examples of this class of compounds, that entered Phase II clinical trials, are NAMI-A and KP1019. During the last decade other structuraly different ruthenium compounds have been synthesized with auspicious results. Our research group has been engaged in the synthesis of new ruthenium compounds based on the [RuII(�?·5-C5H5)(PP)(L)]+ structure (PP=monodentate or bidentate phosphane; L=monodentate or bidentate heteroaromatic ligand) that proved to have, in most cases, lower IC50 than cisplatin. There are many factors that modulate the cytotoxic activity of Ru-based drugs and seem to be dependent on the family compounds under scrutiny. We are interested in pinpointing/understanding whether (and how) structural factors control and potentiate the anti-tumor activity of ruthenium-cyclopentadienyl complexes. In this frame, the structureâ�?�?activity performance of a new family of complexes of general formula [RuII(�?·5-C5H5)(bipy)(L)][PF6] (bipy=2,2â�?�?-bipyridine; L=imidazole; 1-benzyl-1-imidazole; 4-(1H-imidazol-1-yl)phenol; 1-(4-methoxyphenol)-1H-imidazole; dimethyl sulfoxide; carbon monoxide and triphenylphosphane) was designed using TM34, [RuII(�?·5-C5H5)(bipy)(PPh3)][CF3SO3][6], as a model. Thus, the introduction of coligand diversity was achieved by Ï�?-coordination of different atoms, namely N, S, C and P. In addition, the precursor of these compounds, [RuII(�?·5-C5H5)(bipy)(NCCH3)][PF6] was isolated and characterized for comparison and better understanding of the spectroscopic and electrochemical data.

Biography :

Email: leonorcreal@gmail.com