Javier E Ortiz1, Adriana Garro2, Natalia B Pigni3, María Belén Agüero1, German Roitman4, Alberto Slanis5, Ricardo D Enriz2, Gabriela E Feresin1, Jaume Bastida6, Alejandro Tapia7. 1. Instituto de Biotecnología-Instituto de Ciencias Básicas, CONICET, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martín 1109 (O), San Juan CP 5400, Argentina. 2. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, San Luis 5700, Argentina. 3. ICYTAC-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina; Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, Barcelona 08028, Spain. 4. Cátedra de Jardinería, Facultad de Agronomía, Universidad de Buenos Aires, Av. San Martín 4453, Buenos Aires 1417, Argentina. 5. Facultad de Ciencias Naturales e Instituto Miguel Lillo, Universidad Nacional de Tucumán, Fundación Miguel Lillo 251, Tucumán, Argentina. 6. Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, Barcelona 08028, Spain. 7. Instituto de Biotecnología-Instituto de Ciencias Básicas, CONICET, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martín 1109 (O), San Juan CP 5400, Argentina. Electronic address: atapia@unsj.edu.ar.
Abstract
BACKGROUND: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD). PURPOSE: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts. STUDY DESIGN AND METHODS: AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out. RESULTS: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC50 = 1.84 - 15.40 µg/ml) and moderate BChE (IC50 = 23.74 - 136.40 µg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities. CONCLUSION: Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.
BACKGROUND: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD). PURPOSE: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts. STUDY DESIGN AND METHODS: AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out. RESULTS: Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC50 = 1.84 - 15.40 µg/ml) and moderate BChE (IC50 = 23.74 - 136.40 µg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities. CONCLUSION: Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.
Authors: Anna Hudcová; Aleš Kroutil; Renata Kubínová; Adriana D Garro; Lucas J Gutierrez; Daniel Enriz; Michal Oravec; Jozef Csöllei Journal: Molecules Date: 2020-04-10 Impact factor: 4.411