Alkaloids from Hippeastrum argentinum and Their Cholinesterase-Inhibitory Activities: An in Vitro and in Silico Study.
Two new alkaloids, 4-O-methylnangustine (1) and 7-hydroxyclivonine (2) (montanine and homolycorine types, respectively), and four known alkaloids were isolated from the bulbs of Hippeastrum argentinum, and their cholinesterase-inhibitory activities were evaluated. These compounds were identified using GC-MS, and their structures were defined by physical data analysis. Compound 2 showed weak butyrylcholinesterase (BuChE)-inhibitory activity, with a half-maximal inhibitory concentration (IC50) value of 67.3 ± 0.09 μM. To better understand the experimental results, a molecular modeling study was also performed. The combination of a docking study, molecular dynamics simulations, and quantum theory of atoms in molecules calculations provides new insight into the molecular interactions of compound 2 with BuChE, which were compared to those of galantamine.
Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan , Avenida Libertador General San Martín 1109 (O), 5400 San Juan, Argentina.
Javier E
JE
Ortiz
Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona , Avenida Joan XXIII s/n, 08028 Barcelona, Spain.|ICYTAC-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , 5000 Córdoba, Argentina.
Natalia B
NB
Pigni
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis , Chacabuco 915, 5700 San Luis, Argentina.
Sebastián A
SA
Andujar
Cátedra de Jardinería, Facultad de Agronomía, Universidad de Buenos Aires , Avenida San Martín 4453, 1417 Buenos Aires, Argentina.
German
G
Roitman
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis , Chacabuco 915, 5700 San Luis, Argentina.
Fernando D
FD
Suvire
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis , Chacabuco 915, 5700 San Luis, Argentina.
Ricardo D
RD
Enriz
Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan , Avenida Libertador General San Martín 1109 (O), 5400 San Juan, Argentina.
Alejandro
A
Tapia
Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona , Avenida Joan XXIII s/n, 08028 Barcelona, Spain.
Jaume
J
Bastida
Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan , Avenida Libertador General San Martín 1109 (O), 5400 San Juan, Argentina.
Gabriela E
GE
Feresin
D047151:Amaryllidaceae Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001118:Argentina; D002091:Butyrylcholinesterase / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018517:Plant Roots / Q000737:chemistry
C000619004:4-O-methylnangustine; C000619005:7-hydroxyclivonine; D047151:Amaryllidaceae Alkaloids; C057585:homolycorine; D002091:Butyrylcholinesterase