Synthesis of novel flavone hydrazones: In-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies

Imran, Syahrul; Taha, Muhammad; Ismail, Nor Hadiani; Kashif, Syed Muhammad; Rahim, Fazal; Jamil, Waqas; Hariono, Maywan; Yusuf, Muhammad; Wahab, Habibah A.

doi:10.1016/j.ejmech.2015.10.017

Cited by 125 publications

(51 citation statements)

References 60 publications

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“…[37] However, all of these compounds are much more effective than the standard acarbose (IC 50 = 51.32 mm). [38] Additionally, any modification to the 4'-hydroxy group induces al oss in a-glucosidase inhibitory activity,w hereas modification to the 5-hydroxy group results in moderate activity.B eyond that, some synthetic flavones such as compound 71 with other substituents at the 4'-positiona re also good inhibitors against baker's yeast a-glucosidase, [39] and nitroxy alkylation of the hydroxy group at the C7 position or C4' positiong ives compounds 72 and 73 with increased inhibitory activity as ar esult of the formation of new hydrogen bonds. [38] Additionally, any modification to the 4'-hydroxy group induces al oss in a-glucosidase inhibitory activity,w hereas modification to the 5-hydroxy group results in moderate activity.B eyond that, some synthetic flavones such as compound 71 with other substituents at the 4'-positiona re also good inhibitors against baker's yeast a-glucosidase, [39] and nitroxy alkylation of the hydroxy group at the C7 position or C4' positiong ives compounds 72 and 73 with increased inhibitory activity as ar esult of the formation of new hydrogen bonds.…”

Section: Chromonesmentioning

confidence: 90%

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Recent Advances in Synthetic α‐Glucosidase Inhibitors

Liu

2017

ChemMedChem

116

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Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs have been proven to have many advantages over other drugs, and therefore, a large number of new compounds as α-glucosidase inhibitors has recently been reported. In this review, we summarize these newly found α-glucosidase inhibitors and their structure-activity relationships in antidiabetic studies and provide better structures for α-glucosidase inhibitors or even preclinical candidates. Beyond that, some enlightening strategies for the synthesis of relevant compounds are highlighted.

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Section: Chromonesmentioning

confidence: 90%

“…[43] Amongt he derivatives, compound 79 showst he highest inhibitory activity against baker's yeast a- Table 7. [37][38][39][40][41] glucosidase. [37][38][39][40][41] glucosidase.…”

Section: Macrocyclic Compoundsmentioning

confidence: 99%

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Liu

2017

ChemMedChem

116

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“…The construction and optimization of the SBVS protocol to identify potent AChE inhibitors employed potent AChE inhibitors with IC50 value of less than 1 M and their decoys organized and stored in DUD-E (Mysinger et al, 2012) as the retrospective compounds for the validation. Chalcone derivatives were selected since the synthesis expertise in the field is accessible for further investigation in the subsequent discovery and development process (Imran et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Active AChE inhibitors (453) and the decoys (26,350) from DUD-E (Mysinger et al, 2012) were employed to perform retrospective validations for the SBVS protocol. Chalcone derivatives inspired from Imran et al (Imran et al, 2015) which were designed manually (Table I) were used as entry points for lead compounds selection. All calculations and computational simulations were performed on a Linux (Ubuntu 12.04 LTS Precise Pangolin) machine with Intel (R) Xeon (R) CPU E31220 (@ 3.10GHz) as the processors and 8.00GB of RAM.…”

Section: Methodsmentioning

confidence: 99%

Computer-aided Design of Chalcone Derivatives as Lead Compounds Targeting Acetylcholinesterase

Riswanto

Hariono

Yuliani

et al. 2017

Indonesian J. Pharm.

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One of well-established biological activities for chalcone derivatives is as acetylcholinesterase inhibitors, which can be developed for the therapy of Alzheimer's disease. Assisted by retrospectively validated structure-based virtual screening (SBVS) protocol to identify potent acetylcholinesterase inhibitors, 80 chalcone derivatives were designed and virtually screened. The F-measure value as the parameter of the predictive ability of the SBVS protocol developed in the research presented in this article was 0.413, which was considerably better than the original SBVS protocol (Fmeasure=0.226). Among the screened chalcone derivatives two were selected as potential lead compounds to design potent inhibitors for acetylcholinesterase: 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxy-3-methoxy-phenyl)prop-2-en-1-one(3k) and 3-[4-(benzyloxy)-3-methoxyphenyl]-1-(4-hydroxyphenyl)prop-2-en-1-one (4k).

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“…α‐Glucosidase (EC 3.2.1.20), a carbohydrate‐hydrolase commonly found in small intestine, can specifically hydrolyze 1, 4‐α‐glycosidic bond and release α‐ d ‐glucose into the blood stream during food digestion . The proper reduction of digestion and absorption of glucose by inhibiting α‐glucosidase may be an effective strategy to treat T2DM, hyperlipidemia, and obesity .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of novel N‐aryl‐ω‐(benzoazol‐2‐yl)‐sulfanylalkanamides as dual inhibitors of α‐glucosidase and protein tyrosine phosphatase 1B

et al. 2018

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α-Glucosidase is known to catalyze the digestion of carbohydrates and release free glucose into the digestive tract. Protein tyrosine phosphatase 1B (PTP1B) is engaged in the dephosphorylation of the insulin receptor and regulation of insulin sensitivity. Therefore, dual antagonists by targeting both α-glucosidase and PTP1B may be potential candidates for type 2 diabetes therapy. In this work, three series of novel N-aryl-ω-(benzoazol-2-yl)-sulfanylalkanamides were synthesized and assayed for their α-glucosidase and PTP1B inhibitory activities, respectively. Compound 3l, exhibiting the most effective α-glucosidase inhibitory activity (IC = 10.96 μm (3l), IC = 51.32 μm (Acarbose), IC = 18.22 μm (Ursolic acid)) and potent PTP1B inhibitory activity (IC = 13.46 μm (3l), IC = 14.50 μm (Ursolic acid)), was identified as a novel dual inhibitor of α-glucosidase and PTP1B. Furthermore, 3l is a highly selective PTP1B inhibitor because no inhibition was showed by 3l at 100 μm against PTP-MEG2, TCPTP, SHP2, or SHP1. Subsequent kinetic analysis revealed 3l inhibited α-glucosidase in a reversible and mixed manner. Molecular docking study indicated that hydrogen bonds, van der Waals, charge interactions and Pi-cation interactions all contributed to affinity between 3l and α-glucosidase/PTP1B.

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Synthesis of novel flavone hydrazones: In-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies

Cited by 125 publications

References 60 publications

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Recent Advances in Synthetic α‐Glucosidase Inhibitors

Computer-aided Design of Chalcone Derivatives as Lead Compounds Targeting Acetylcholinesterase

Synthesis and biological evaluation of novel N‐aryl‐ω‐(benzoazol‐2‐yl)‐sulfanylalkanamides as dual inhibitors of α‐glucosidase and protein tyrosine phosphatase 1B

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