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Title: Feruloyl sucrose esters: potent and selective inhibitors of α-glucosidase and α-amylase
Authors: Devaraj, Surabhi
Yip, Yew Mun
Panda, Parthasarathi
Ong, Li Lin
Wong, Kathy Pooi Wen
Zhang, Dawei
Ali, Yusuf
Judeh, Zaher
Keywords: Science::Medicine
Issue Date: 2022
Source: Devaraj, S., Yip, Y. M., Panda, P., Ong, L. L., Wong, K. P. W., Zhang, D., Ali, Y. & Judeh, Z. (2022). Feruloyl sucrose esters: potent and selective inhibitors of α-glucosidase and α-amylase. Current Medicinal Chemistry, 29(9), 1606-1621.
Project: 2019- T1-001-059
Journal: Current Medicinal Chemistry
Abstract: Abstract: Introduction: Feruloyl Sucrose Esters (FSEs) are a class of Phenylpropanoid Sucrose Esters (PSEs) widely distributed in plants. They were investigated as potential selective Alpha Glucosidase Inhibitors (AGIs) to eliminate the side effects associated with the current commercial AGIs. The latter effectively lowers blood glucose levels in diabetic patients but causes severe gastrointestinal side effects. Methods: Systematic structure-activity relationship (SAR) studies using in silico, in vitro and in vivo experiments were used to accomplish this aim. FSEs were evaluated for their in vitro inhibition of starch and oligosaccharide digesting enzymes α-glucosidase and α amylase followed by in silico docking studies to identify the binding modes. A lead candidate, FSE 12 was investigated in an STZ mouse model. Results: All active FSEs showed desired higher % inhibition of α-glucosidase and desired lower inhibition of α -amylase in comparison to AGI gold standard acarbose. This suggests a greater selectivity of the FSEs towards α -glucosidase than α -amylase, which is proposed to eliminate the gastrointestinal side effects. From the in vitro studies, the position and number of the feruloyl substituents on the sucrose core, the aromatic ‘OH’ group, and the diisopropylidene bridges were key determinants of the % inhibition of α - glucosidase and α -amylase. In particular, the diisopropylidene bridges are critical for achieving inhibition selectivity. Molecular docking studies of the FSEs corroborates the in vitro results. The molecular docking studies further reveal that the presence of free aromatic ‘OH’ groups and the substitution at position 3 on the sucrose core are critical for the inhibition of both the enzymes. From the in vitro and molecular docking studies, FSE 12 was selected as a lead candidate for validation in vivo. The oral co-administration of FSE 12 with starch abrogated the increase in post-prandial glucose and significantly reduced blood glucose excursion in STZ-treated mice compared to control (starch only) mice. Conclusion: Our studies reveal the potential of FSEs as selective AGIs for the treatment of diabetes, with a hypothetical reduction of side effects associated with commercial AGIs.
ISSN: 0929-8673
DOI: 10.2174/0929867328666210827102456
Schools: School of Chemical and Biomedical Engineering 
School of Physical and Mathematical Sciences 
Interdisciplinary Graduate School (IGS) 
Lee Kong Chian School of Medicine (LKCMedicine) 
Research Centres: NTU Institute for Health Technologies 
Rights: © 2022 Bentham Science Publishers. All rights reserved. This paper was published in Current Medicinal Chemistry and is made available with permission of Bentham Science Publishers.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:IGS Journal Articles
LKCMedicine Journal Articles
SCBE Journal Articles
SPMS Journal Articles

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