Synthesis and anticancer activity of N3-substituted-6,8-diaminopurines

[Excerpt] Cancer is the second most common cause of death in developed countries appearing just after cardiovascular diseases. The treatment of cancer remains a major medical challenge and the development of new anticancer drugs is an emerging topic for the scientific community. During the past three decades several chemical classes of anticancer drugs have been identified. In particular, 2,6-diamino purines proved to be important candidates as new anti-cancer agents.

A new and efficient synthesis of N3-cycloalkylamino-6,8-diaminopurines

[Excerpt] The purine core is a privileged scaffold in medicinal chemistry and the biological relevance of purine derivatives makes them attractive targets in the preparation of combinatorial libraries.1,2 In particular, there is a great interest in the synthesis of 8-substituted purines due to their important potential as antiviral and anticancer agents.3 Reports on 8-aminopurines are limited and general methods to obtain these purine derivatives are still needed.4 Cyclic amines and hydrazines are key structural motifs in various bioactive agents.5 Here we report a novel, efficient and inexpensive method for the synthesis of 6,8-diaminopurines 4 incorporating cycloalkylamino substituents at N3position of the purine ring. (...)

A novel and efficient approach to new N3-substituted-6,8-diaminopurines

[Excerpt] Purine nucleobases are fundamental biochemicals in living organisms. They have been a valuable inspiration for drug design once they play several key roles in the cell.1 To the best of our knowledge, reported routes to 8-aminopurines are still scarce due to the difficulty in introducing amino groups in this position of the purine ring. Here we report a novel, inexpensive and facile synthetic method to generate N3,N6-disubstituted-6,8-diaminopurines. In our research group, a number of substituted purines have been obtained from a common imidazole precursor, the 5-amino-4-cyanoformimidoyl imidazole 1. Recently, a comprehensive study on the reactivity of imidazoles 1 with nucleophiles under acidic conditions led us to develop experimental methods to incorporate primary amines into the cyanoformimidoyl group.2 (...)

A VEP study in sleeping and awake one-month-old infants and its relation with social behavior

With the present study we aimed to analyze the relationship between infants' behavior and their visual evoked-potential (VEPs) response. Specifically, we want to verify differences regarding the VEP response in sleeping and awake infants and if an association between VEP components, in both groups, with neurobehavioral outcome could be identified. To do so, thirty-two full-term and healthy infants, approximately 1-month of age, were assessed through a VEP unpatterned flashlight stimuli paradigm, offered in two different intensities, and were assessed using a neurobehavioral scale. However, only 18 infants have both assessments, and therefore, these is the total included in both analysis. Infants displayed a mature neurobehavioral outcome, expected for their age. We observed that P2 and N3 components were present in both sleeping and awake infants. Differences between intensities were found regarding the P2 amplitude, but only in awake infants. Regression analysis showed that N3 amplitude predicted an adequate social interactive and internal regulatory behavior in infants who were awake during the stimuli presentation. Taking into account that social orientation and regulatory behaviors are fundamental keys for social-like behavior in 1-month-old infants, this study provides an important approach for assessing physiological biomarkers (VEPs) and its relation with social behavior, very early in postnatal development. Moreover, we evidence the importance of the infant's state when studying differences regarding visual threshold processing and its association with behavioral outcome.

Síntese de derivados de adenina e guanina

Tese de Doutoramento em Ciências (Especialidade em Química)