Antidiabetic xanthones with α-glucosidase inhibitory activities from an endophytic Penicillium canescens
(2020) In Fitoterapia 142. p.104522-104522- Abstract
Worldwide, 463 million people are affected by diabetes of which the majority is diagnosed with Type 2 Diabetes (T2D). T2D can ultimately lead to retinopathy, nephropathy, nerve damage, and amputation of the lower extremities. α-Glucosidase, responsible for converting starch to monosaccharides, is a key therapeutic target for the management of T2D. However, due to substantial side effects of currently marketed drugs, there is an urgent need for the discovery of new α-glucosidase inhibitors. In our ongoing efforts to identify novel α-glucosidase inhibitors from Nature, we are investigating the potential of endophytic filamentous fungi as sustainable sources of hits and/or leads for future antihyperglycemic drugs. Here we report one... (More)
Worldwide, 463 million people are affected by diabetes of which the majority is diagnosed with Type 2 Diabetes (T2D). T2D can ultimately lead to retinopathy, nephropathy, nerve damage, and amputation of the lower extremities. α-Glucosidase, responsible for converting starch to monosaccharides, is a key therapeutic target for the management of T2D. However, due to substantial side effects of currently marketed drugs, there is an urgent need for the discovery of new α-glucosidase inhibitors. In our ongoing efforts to identify novel α-glucosidase inhibitors from Nature, we are investigating the potential of endophytic filamentous fungi as sustainable sources of hits and/or leads for future antihyperglycemic drugs. Here we report one previously unreported xanthone (5) and two known xanthones (7 and 11) as α-glucosidase inhibitors, isolated from an endophytic Penicillium canescens, recovered from fruits of Juniperus polycarpos. The three xanthones 5, 7, and 11 showed inhibitory activities against α-glucosidase with IC50 values of 38.80 ± 1.01 μM, 32.32 ± 1.01 μM, and 75.20 ± 1.02 μM, respectively. Further pharmacological characterization revealed a mixed-mode inhibition for 5, a competitive inhibition for 7, while 11 acted as a non-competitive inhibitor.
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- author
- Malik, Abd ; Ardalani, Hamidreza LU ; Anam, Syariful ; McNair, Laura Mikél ; Kromphardt, Kresten J. K. ; Frandsen, Rasmus John Normand ; Franzyk, Henrik ; Staerk, Dan and Kongstad, Kenneth T.
- publishing date
- 2020-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Drug Evaluation, Preclinical, Endophytes/chemistry, Glycoside Hydrolase Inhibitors/chemistry, Juniperus/microbiology, Penicillium/chemistry, Xanthones/chemistry
- in
- Fitoterapia
- volume
- 142
- pages
- 104522 - 104522
- publisher
- Elsevier
- external identifiers
-
- scopus:85081231276
- pmid:32088281
- ISSN
- 0367-326X
- DOI
- 10.1016/j.fitote.2020.104522
- language
- English
- LU publication?
- no
- id
- 5333a698-3931-4702-ba32-99b240a4bc86
- date added to LUP
- 2021-05-13 14:16:07
- date last changed
- 2024-03-23 04:33:43
@article{5333a698-3931-4702-ba32-99b240a4bc86,
abstract = {{<p>Worldwide, 463 million people are affected by diabetes of which the majority is diagnosed with Type 2 Diabetes (T2D). T2D can ultimately lead to retinopathy, nephropathy, nerve damage, and amputation of the lower extremities. α-Glucosidase, responsible for converting starch to monosaccharides, is a key therapeutic target for the management of T2D. However, due to substantial side effects of currently marketed drugs, there is an urgent need for the discovery of new α-glucosidase inhibitors. In our ongoing efforts to identify novel α-glucosidase inhibitors from Nature, we are investigating the potential of endophytic filamentous fungi as sustainable sources of hits and/or leads for future antihyperglycemic drugs. Here we report one previously unreported xanthone (<b>5</b>) and two known xanthones (<b>7</b> and <b>11</b>) as α-glucosidase inhibitors, isolated from an endophytic Penicillium canescens, recovered from fruits of <i>Juniperus polycarpos</i>. The three xanthones <b>5</b>, <b>7</b>, and <b>11</b> showed inhibitory activities against α-glucosidase with IC50 values of 38.80 ± 1.01 μM, 32.32 ± 1.01 μM, and 75.20 ± 1.02 μM, respectively. Further pharmacological characterization revealed a mixed-mode inhibition for <b>5</b>, a competitive inhibition for <b>7</b>, while <b>11</b> acted as a non-competitive inhibitor.</p>}},
author = {{Malik, Abd and Ardalani, Hamidreza and Anam, Syariful and McNair, Laura Mikél and Kromphardt, Kresten J. K. and Frandsen, Rasmus John Normand and Franzyk, Henrik and Staerk, Dan and Kongstad, Kenneth T.}},
issn = {{0367-326X}},
keywords = {{Drug Evaluation, Preclinical; Endophytes/chemistry; Glycoside Hydrolase Inhibitors/chemistry; Juniperus/microbiology; Penicillium/chemistry; Xanthones/chemistry}},
language = {{eng}},
pages = {{104522--104522}},
publisher = {{Elsevier}},
series = {{Fitoterapia}},
title = {{Antidiabetic xanthones with α-glucosidase inhibitory activities from an endophytic <i>Penicillium canescens</i>}},
url = {{http://dx.doi.org/10.1016/j.fitote.2020.104522}},
doi = {{10.1016/j.fitote.2020.104522}},
volume = {{142}},
year = {{2020}},
}