Two alkaloids as α-amylase inhibitors: enzyme kinetics and molecular modeling investigations

doi:10.5246/jcps.2015.02.009

Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (2): 80-87.DOI: 10.5246/jcps.2015.02.009

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Two alkaloids as α-amylase inhibitors: enzyme kinetics and molecular modeling investigations

Yi Liang¹, Fen Pei², Hong Wang^1*, Shizhong Chen^1*

1. Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2014-06-30 Revised:2014-09-28 Online:2015-02-01 Published:2014-11-24
Contact: Tel./Fax: 86-10-82802723, 86-10-82801559
Supported by:
State Key Laboratory of Natural and Biomimetic Drugs 2013 Funded Project “Establishment and Application an Online Natural Medicines System with Efficient Separation, Structural Identification and Activity Detection”.

Abstract

Abstract:

In the present study, we studied the inhibitory effects of chelidonine and rutaecarpin on porcine pancreatic α-amylase (PPA) catalyzed hydrolysis using 2-chloro-4-nitrophenyl-4-O-β-D-galactopyranosylmaltoside (Gal-G2-α-CNP). We, for the first time, provided kinetic report and detailed inhibitory effects of both compounds on PPA. Lineweaver-Burk plot revealed that the inhibition was a mixed-noncompetitive type, and only one molecule of inhibitor bound to the enzyme or to the enzyme-substrate complex. Kinetic constants calculated from secondary plots were in millimole range. Dissociation constants of enzyme-inhibitor complex (K_EI) were 0.9 mM and 3.5 mM, respectively. Moreover, dissociation constants of enzyme-inhibitor-substrate complex (K_E_SI) were 0.04 mM and 0.31 mM, respectively. These data indicated that the inhibition was more inclined to competitive to Gal-G2-α-CNP hydrolysis. Further molecular docking study manifested that hydrogen bonding formed between acarbose and aspartic acid (Asp³⁰⁰), histidine (His³⁰⁵) and glycine (Gly³⁰⁶), while hydrogen bonding was observed between chelidonine and glutamic acid (Glu²³³), lysine (Lys²⁰⁰) and His³⁰⁵. In addition, rutaecarpine had only one hydrogen bond with Lys²⁰⁰. Our data indicated that chelidonine and rutaecarpine were two promising drug candidates, and chelidonine possessed stronger inhibitory effect compared with rutaecarpine.

Key words: α-Amylase inhibitors, Kinetic analysis, Molecular modeling, Chelidonine, Rutaecarpine

CLC Number:

R917

Supporting:

Yi Liang, Fen Pei, Hong Wang, Shizhong Chen. Two alkaloids as α-amylase inhibitors: enzyme kinetics and molecular modeling investigations[J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(2): 80-87.

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Two alkaloids as α-amylase inhibitors: enzyme kinetics and molecular modeling investigations

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