Propriedades estruturais e eletrônicas de análogos da acridina

Abstract

The Cancer is a growing worldwise problem and has shown an epidemiological profile. Informations about the carcinogenic mechanisms configure themselves as important tools in cancer control and prevention. The understanding of structure-activity relationships in compounds who present biological activity is highly relevant on the investigation of the carcinogenic compounds behavior in molecular systems and in the activity-optimized drugs developing. We performed an study of the eletronic properties from 14 acridine similar compounds. These compounds were former studied by Cuny et al and within an esperimental study with the TR-FRET thecnique (Time-Resolved Florescence Resonance Energy Transfer), and were classified as potent inibitors of two enzymes, Haspin and DYRK2, who had part on the conclusion mitosis process in several cells, inclusive cancerigen cells. The main objective of the present work was establish a relationship between obtanied data from the calculations of eletronic properties and the experimentally obtanied data with the aim of classify these compounds regarding it's biological activite, within the eletronic indices motodology ( EIM ). The geometric otimization, as the eletronic structure calculations, were made by the semi-empiric methody AM1 and PM3, by the DFT ab initio methody. For these calculations, we used firstly the software Spartan as visual tool and for the conformational analisys, then, the calculations were made with the GAMESS program. After the geometry was optimized, we used the Chem2pac in order to calculate the state local density. The PCA and HCA studies were performed by the Eeinsigth program. Th-rough the EIM parameters we established simple rules, with which we identified precisely the active and inactive compounds. In the investigations EIM, PCA and HCA, the acridine analogous activity was correlated with the theoretical parameters. The eletronic parameters found by EIM showed themselves largely important for others pattern recognition metodologies.