RESUMO
Biological membranes play an essential role in the drug action. They constitute the first barrier for drugs to exert their biological action. AT1 antagonists are amphiphilic molecules and are hypothesized to act on AT1 receptor through incorporation (first step) and lateral diffusion through membrane bilayers (second step). Various biophysical methods along with Molecular Modelling were applied in order to explore the plausible two step proposed mechanism of action for this class of antihypertensive drugs.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Membrana Celular/efeitos dos fármacos , Aminoácidos/química , Aminoácidos/metabolismo , Anti-Hipertensivos/uso terapêutico , Sítios de Ligação , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Varredura Diferencial de Calorimetria , Membrana Celular/química , Membrana Celular/metabolismo , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Imidazóis/química , Imidazóis/farmacologia , Irbesartana , Losartan/química , Losartan/farmacologia , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Receptor Tipo 1 de Angiotensina/química , Tetrazóis/química , Tetrazóis/farmacologia , Difração de Raios XRESUMO
The structure of 11-benzoyl-9,9a,10,11-tetrahydro-4H-indolo [4,3-ab] carbazole, a candidate molecule to possess significant antitumor or antimicrobial activity, was elucidated using a combination of one-dimensional and two-dimensional nuclear magnetic resonance (NMR) techniques. Its conformational properties were studied using a combination of two-dimensional NOESY spectroscopy and molecular modeling. Such information will be of aid to synthetic chemists who aim to develop derivatives of this structure. It may also provide information about the stereoelectronic requirements that govern their activities.
