High throughput artificial membrane permeability assay for blood–brain barrier

Shogaol–huprine hybrids: Dual antioxidant and anticholinesterase agents with β-amyloid and tau anti-aggregating properties

“…Assay validation was made by comparison of the experimental P e values of the known drugs with their reported values, which showed a good correlation: P e (exp) = 1.5605 P e (lit) -1.0507 (R 2 = 0.9308). From this equation and the limits established by Di et al for BBB permeation, 46 three ranges of permeability were established: compounds of high BBB permeation (CNS+): P e (10 −6 cm s −1 ) > 5.19; compounds of low BBB permeation (CNS-): P e (10 −6 cm s −1 ) < 2.07; and compounds of uncertain BBB permeation (CNS+/-): 5.19 > P e (10 −6 cm s −1 ) > 2.07. …”

“…46 The in vitro permeability (P e ) of the shogaol-huprine hybrids, the parent compounds huprine Y and [4]-shogaol, and 14 commercial drugs, the later used for assay validation ( 46 it was established that compounds with P e (10 −6 cm s −1 ) > 5.2 would have high BBB permeation (CNS+) and compounds with P e (10 −6 cm s −1 ) < 2.1 would have low BBB permeation (CNS−).…”

“…The in vitro permeability (P e ) of the novel hybrids and fourteen known drugs through lipid extract of porcine brain membrane was determined by using a parallel artificial membrane permeation assay, 46 using a mixture PBS:EtOH 70:30. Assay validation was made by comparison of the experimental P e values of the known drugs with their reported values, which showed a good correlation: P e (exp) = 1.5605 P e (lit) -1.0507 (R 2 = 0.9308).…”

Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment

“…In order to predict passive blood-brain penetration of most promising compounds prepared in the current study (10, 17, 21), a modification of the parallel artificial membrane permeation assay (PAMPA) has been used based on reported protocol. 54 The penetration value (P e ) was derived mathematically from time-dependent changes of the selected compounds' concentrations in two aqueous phases separated by the artificial membrane (see Experimental section). Compounds 10 and 17 showed P e values greater than 4, which indicate sufficient passive transition of the compounds through the BBB (Table 3).…”

Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines

“…The BBB permeability of bis-huprines (+)-2a-e was assessed in vitro through the widely used parallel artificial membrane permeability assay (PAMPA-BBB), using a lipid extract of porcine brain as the artificial membrane. 37 Assay validation was performed by comparing the experimentally observed permeabilities [P e (exp)] of fourteen marketed drugs with the permeabilities reported in the literature [P e (lit)], which provided a good linear correlation: P e (exp) = 1.4974 P e (lit) -0.8434 (R 2 = 0.9428). Taking into account this equation and the limits established by Di et al, 35 three ranges of BBB permeation were established: high BBB permeation (CNS+) for those compounds with P e (10 -6 cm s -1 ) > 5.1; low BBB permeation (CNS-) for those compounds with P e (10 -6 cm s -1 ) < 2.1; and uncertain BBB permeation (CNS±) for those compounds with 5.1 > P e (10 -6 cm s -1 ) > 2.1.…”