Carla Santana Francisco

Tacrine and its analogues impair mitochondrial function and bioenergetics : a lipidomic analysis in rat brain

J. Neurochem. (2012) 120, 993–1013.

Synthesis of novel benzofurocoumarin analogues and their anti-proliferative effect on human cancer cell lines

The synthesis of five new tetracyclic benzofurocoumarin (benzopsoralen) analogues is described. Their inhibitory effects on the growth of three human tumor cell lines (MDA MB 231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma) were evaluated, and discussed in terms of structure-activity relationship.

Synthesis of Tacrine Analogs Derived from N-Aryl-5-amino-4-cyanopyrazoles

Abstract Synthesis of 11 tacrine analogs derived from N-aryl-5-amino-4-cyanopyrazoles, by a Friedländer type reaction, is described. Their structures were confirmed by 1H and 13C NMR spectroscopy, elemental analysis, and/or mass spectrometry.

Synthesis of novel psoralen analogues and their in vitro antitumor activity

New tetracyclic benzofurocoumarin (benzopsoralen) analogues were synthesized and their inhibitory effect on the growth of tumor cell lines was evaluated. The human tumor cell lines used were MDA MB231 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and TCC-SUP (bladder transitional cell carcinoma). The in vitro antitumor activity of the new benzopsoralens was discussed in terms of structure-activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds in order to evaluate the potential of these compounds to interact with the heme group of the enzymes. The results have demonstrated that the linear compounds have the most pronounced activity against tumor cell lines and this might be related to the better accessibility that these compounds have to the active site in relation to the angular ones that have shown in the majority of the cases multiple binding poses in the active site of CYP2A6.

Novel benzopsoralen analogues: Synthesis, biological activity and molecular docking studies

New benzopsoralen analogues were synthesized and their inhibitory effect on the growth of tumourtumour cell lines (MDA MB231 and TCC-SUP) was evaluated. The in vitro antitumour activity of the new benzopsoralen analogues was discussed in terms of structure-activity relationship. Molecular docking studies with human-CYP2A6 enzymes were also carried out with the synthesized compounds to evaluate the potential of these molecules to interact with the haem group of the enzymes. The results demonstrated that the compounds that are able to interact with the iron ion of the haem cofactor and at the same time with active site Asn297 are those that have better anti-proliferative activity.

DOENÇA DE HANSEN E GRAVIDEZ

A Doenca de Hansen e uma doenca infecciosa causada pelo microrganismo Mycobacterium leprae. No passado, a gravidade da apresentacao desta doenca e a inexistencia de terapeutica adequada, levou a estigmatiza- cao destes doentes. Felizmente, a forma com se olha esta patologia melhorou nas ultimas decadas gracas a terapeu- tica multipla que agora temos ao nosso dispor. Com o fenomeno da imigracao de regioes do globo onde esta doenca ainda tem uma prevalencia significativa, assis- timos ao surgimento de novos casos de Lepra em Portugal, nomeadamente em mulheres em idade fertil. A doenca de Hansen na gravidez coloca questoes quer no que respeita as consequencias da terapeutica (durante a gravidez e amamentacao), quer no que se refere ao momento do parto. A gravidez causa uma diminuicao relativa da imunidade celular, o que permite a proliferacao do bacilo com possivel agravamento da doenca. A escolha dos farmacos adequados impede a lesao nervosa permanente. Relatam-se tres casos seguidos na Maternidade Dr. Alfredo da Costa, em conjunto com o servico de Dermatologia do Hospital Curry Cabral, que pretendem ilustrar a vigilância da gravidez nestas situacoes. Em todos eles as gravidas foram medicadas com rifampicina e clofazimina. Esta reflexao sobre Gravidez e Lepra visa desmistificar a patologia e sublinhar a importância do seguimento multidis- ciplinar destas gestacoes. PALAVRAS-CHAVE – Gravidez; Clofazimina; Rifampicina; Lepra.