TY - JOUR
T1 - Alkaloids of Amaryllidaceae as Inhibitors of Cholinesterases (AChEs and BChEs)
T2 - An Integrated Bioguided Study
AU - Cortes, Natalie
AU - Sierra, Karina
AU - Alzate, Fernando
AU - Osorio, Edison H.
AU - Osorio, Edison
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Introduction: Enzymatic inhibition of acetylcholinesterase (AChE) is an essential therapeutic target for the treatment of Alzheimer's disease (AD) and AChE inhibitors are the first-line drugs for it treatment. However, butyrylcholinesterase (BChE), contributes critically to cholinergic dysfunction associated with AD. Thus, the development of novel therapeutics may involve the inhibition of both cholinesterase enzymes. Objective: To evaluate, in an integrated bioguided study, cholinesterases alkaloidal inhibitors of Amaryllidaceae species. Methodology: The proposed method combines high-performance thin-layer chromatography (HPTLC) with data analysis by densitometry, enzymatic bioautography with different AChEs and BChEs, the detection of bioactive molecules through gas chromatography mass spectrometry (GC–MS) analysis of spots of interest, and theoretical in silico studies. Results: To evaluate the bioguided method, the AChE and BChE inhibitory activities of seven Amaryllidaceae plant extracts were evaluated. The alkaloid extracts of Eucharis bonplandii exhibited a high level of inhibitory activity (IC50 = 0.72 ± 0.05 μg/mL) against human recombinant AChE (hAChE). Regarding human serum BChE (hBChE), the bulb and leaf extracts of Crinum jagus had the highest activity (IC50 = 8.51 ± 0.56 μg/mL and 11.04 ± 1.21 μg/mL, respectively). In the HPTLC spots with high inhibitory activity, several alkaloids were detected using GC–MS, and some of these alkaloids were identified. Galanthamine, galanthamine N-oxide and powelline should be the most prominent inhibitors of substrate accommodation in the active site of the Torpedo californica AChE (TcAChE), hAChE and hBChE enzymes. Conclusions: These results are evidence of the chemical relevance of the Colombian's Amaryllidaceae species for the inhibition of cholinesterases and as potent sources for the palliative treatment of AD.
AB - Introduction: Enzymatic inhibition of acetylcholinesterase (AChE) is an essential therapeutic target for the treatment of Alzheimer's disease (AD) and AChE inhibitors are the first-line drugs for it treatment. However, butyrylcholinesterase (BChE), contributes critically to cholinergic dysfunction associated with AD. Thus, the development of novel therapeutics may involve the inhibition of both cholinesterase enzymes. Objective: To evaluate, in an integrated bioguided study, cholinesterases alkaloidal inhibitors of Amaryllidaceae species. Methodology: The proposed method combines high-performance thin-layer chromatography (HPTLC) with data analysis by densitometry, enzymatic bioautography with different AChEs and BChEs, the detection of bioactive molecules through gas chromatography mass spectrometry (GC–MS) analysis of spots of interest, and theoretical in silico studies. Results: To evaluate the bioguided method, the AChE and BChE inhibitory activities of seven Amaryllidaceae plant extracts were evaluated. The alkaloid extracts of Eucharis bonplandii exhibited a high level of inhibitory activity (IC50 = 0.72 ± 0.05 μg/mL) against human recombinant AChE (hAChE). Regarding human serum BChE (hBChE), the bulb and leaf extracts of Crinum jagus had the highest activity (IC50 = 8.51 ± 0.56 μg/mL and 11.04 ± 1.21 μg/mL, respectively). In the HPTLC spots with high inhibitory activity, several alkaloids were detected using GC–MS, and some of these alkaloids were identified. Galanthamine, galanthamine N-oxide and powelline should be the most prominent inhibitors of substrate accommodation in the active site of the Torpedo californica AChE (TcAChE), hAChE and hBChE enzymes. Conclusions: These results are evidence of the chemical relevance of the Colombian's Amaryllidaceae species for the inhibition of cholinesterases and as potent sources for the palliative treatment of AD.
KW - acetylcholinesterase
KW - Alzheimer disease
KW - Amaryllidaceae alkaloids
KW - bioautography
KW - butyrylcholinesterase
KW - molecular docking
UR - http://www.scopus.com/inward/record.url?scp=85041385992&partnerID=8YFLogxK
U2 - 10.1002/pca.2736
DO - 10.1002/pca.2736
M3 - Artículo
C2 - 29044771
AN - SCOPUS:85041385992
VL - 29
SP - 217
EP - 227
JO - Phytochemical Analysis
JF - Phytochemical Analysis
SN - 0958-0344
IS - 2
ER -