Oxindole-based chalcones: synthesis and their activity against glycation of proteins
Diabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a maj...
Published in: | Medicinal Chemistry Research |
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Birkhauser Boston
2019
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2-s2.0-85064650678 Khan A.; Khan A.; Farooq U.; Taha M.; Shah S.A.A.; Halim S.A.; Akram A.; Khan M.Z.; Jan A.K.; Al-Harrasi A. Oxindole-based chalcones: synthesis and their activity against glycation of proteins 2019 Medicinal Chemistry Research 28 6 10.1007/s00044-019-02345-1 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064650678&doi=10.1007%2fs00044-019-02345-1&partnerID=40&md5=66c278e82295bf402da68728691f8168 Diabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a major role in the onset of late diabetic complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular diseases. There is a need to establish potential therapeutic regimens that can effectively inhibit the formation of AGEs. To this end a series of novel oxindole-based chalcones have been investigated for their antiglycation potential. Analogues 1 (IC50 = 155.22 ± 2.98 µM), 3 (IC50 = 195.95 ± 0.43 µM), 4 (IC50 = 289.47 ± 2.47 µM), 5 (IC50 = 222.44 ± 4.03 µM), 7 (IC50 = 251.27 ± 2.80 µM), and 20 (224.23 ± 1.93 µM) showed potent inhibitory activity against glycation compared to the reference Rutin (IC50 = 294.5 ± 1.5 µM). These results reveal that multiple hydroxyl substituents and their position on the aromatic ring play a key role in inhibitory effect due to their hydrogen bonding potential. The study also reveals the influence of substituents on the binding capabilities and in turn inhibitory potential of different analogues. © 2019, Springer Science+Business Media, LLC, part of Springer Nature. Birkhauser Boston 10542523 English Article |
author |
Khan A.; Khan A.; Farooq U.; Taha M.; Shah S.A.A.; Halim S.A.; Akram A.; Khan M.Z.; Jan A.K.; Al-Harrasi A. |
spellingShingle |
Khan A.; Khan A.; Farooq U.; Taha M.; Shah S.A.A.; Halim S.A.; Akram A.; Khan M.Z.; Jan A.K.; Al-Harrasi A. Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
author_facet |
Khan A.; Khan A.; Farooq U.; Taha M.; Shah S.A.A.; Halim S.A.; Akram A.; Khan M.Z.; Jan A.K.; Al-Harrasi A. |
author_sort |
Khan A.; Khan A.; Farooq U.; Taha M.; Shah S.A.A.; Halim S.A.; Akram A.; Khan M.Z.; Jan A.K.; Al-Harrasi A. |
title |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
title_short |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
title_full |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
title_fullStr |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
title_full_unstemmed |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
title_sort |
Oxindole-based chalcones: synthesis and their activity against glycation of proteins |
publishDate |
2019 |
container_title |
Medicinal Chemistry Research |
container_volume |
28 |
container_issue |
6 |
doi_str_mv |
10.1007/s00044-019-02345-1 |
url |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064650678&doi=10.1007%2fs00044-019-02345-1&partnerID=40&md5=66c278e82295bf402da68728691f8168 |
description |
Diabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a major role in the onset of late diabetic complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular diseases. There is a need to establish potential therapeutic regimens that can effectively inhibit the formation of AGEs. To this end a series of novel oxindole-based chalcones have been investigated for their antiglycation potential. Analogues 1 (IC50 = 155.22 ± 2.98 µM), 3 (IC50 = 195.95 ± 0.43 µM), 4 (IC50 = 289.47 ± 2.47 µM), 5 (IC50 = 222.44 ± 4.03 µM), 7 (IC50 = 251.27 ± 2.80 µM), and 20 (224.23 ± 1.93 µM) showed potent inhibitory activity against glycation compared to the reference Rutin (IC50 = 294.5 ± 1.5 µM). These results reveal that multiple hydroxyl substituents and their position on the aromatic ring play a key role in inhibitory effect due to their hydrogen bonding potential. The study also reveals the influence of substituents on the binding capabilities and in turn inhibitory potential of different analogues. © 2019, Springer Science+Business Media, LLC, part of Springer Nature. |
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Birkhauser Boston |
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10542523 |
language |
English |
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Article |
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scopus |
collection |
Scopus |
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1809677904536141824 |