Surface active benzodiazepine-bromo- alkyl conjugate for potential GABAA receptor purification

ANAHÍ V. TURINA; GISELA J. QUINTEROS; BENJAMÍN CARUSO; ELIZABETH L. MOYANO; MARÍA A. PERILLO

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: Cambridge; Año: 2011 p. 5737 - 5747

1477-0520

ABSTRACT A conjugable analogue of the benzodiazepine 5-(2-hydroxiphenyl)-7-nitrobenzo[ e][1,4]diazepin-2(3H)-one containing a bromide C12-aliphatic chain (BDC) at nitrogen N1 was synthesized. One-pot preparation of this benzodiazepine derivative was achieved using microwave irradiation giving 49% yield of the desired product. BDC inhibited FNZ binding to GABAA-R with an inhibition binding constant Ki=0.89 μM and expanded a model membrane packed up to 35 mN/m when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure π=9.8 mN/m and minimal molecular area Amin=52 Å2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x≅0.1. A geometrical - thermodynamic analysis along the π-A phase diagram predicted that at low xBDC (