Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis

Wu, Panpan; He, Hao; Ma, Hang; Tu, Borong; Li, Jiahao; Guo, Shengzhu; Chen, Silin; Cao, Nana; Zheng, Wende; Tang, Xiaowen; Li, Dongli; Xu, Xuetao; Zheng, Xi; Sheng, Zhaojun; Hong, W. David; Zhang, Kun

doi:10.1016/j.bioorg.2020.104580

Cited by 22 publications

(12 citation statements)

References 29 publications

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“…All other solvents used in this study were purchased from Aladdin Chemical (Shanghai, China). The Jones reagent was prepared with a method as previously reported 22 . Spectrometer 1 H NMR and 13 C NMR spectra were recorded on a Bruker DPX-500 MHz spectrometer (Bruker Biospin, Rheinstetten, German) with chemical shifts (d) given in parts per million (ppm) with trimethylsilane (TMS) as an internal standard.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability

Akanji

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated (6c) and chlorinated (6g) indole moieties led to enhanced anti-hyaluronidase activity (IC 50 ¼ 80.3 vs. 9.97 and 9.57 mg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH ¼ 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with antihyaluronidase activity.

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Section: Chemicals and Reagentsmentioning

confidence: 99%

Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability

Akanji

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Molecular docking was simulated to show the binding between inhibitor with target protein using Sybyl software (Tripos, US) 21 . The crystal structure of Saccharomyces cerevisiae isomaltase has not been reported, then the homology mode of α-glucosidase was constructed.…”

Section: Methodsmentioning

confidence: 99%

“…The research found that the introduction of oxime-ester moiety into OA can improve its anti-tumour activity 15 , anti-inflammatory effect 16 , the inhibition of HIV-1 protease dimerisation and the inhibitory activity of glycogen phosphorylase compared with the parent compound 17 , 18 and other activities, which was presumably associated with the enhancement of the hydrophilic performance 19 . Furthermore, our group has been dedicated to the structural modification and derivation of OA skeleton at the C2, C3, C12, C13, or C28 position, simultaneously the inhibition of α-glucosidase and its mechanism have been explored in depth 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors

Deng

Zheng

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Different oleanolic acid (OA) oxime ester derivatives ( 3a - 3t ) were designed and synthesised to develop inhibitors against α -glucosidase and α -amylase. All the synthesised OA derivatives were evaluated against α -glucosidase and α -amylase in vitro. Among them, compound 3a showed the highest α -glucosidase inhibition with an IC 50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α -amylase inhibitory with an IC 50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α -glucosidase and α -amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells. Highlights Oleanolic acid oxime ester derivatives ( 3a–3t ) were synthesised and screened against α-glucosidase and α-amylase. Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM. Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM. Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.

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“…[32] Anti SARS-CoV-2 (COVID-19) [33,34] normalise the levels of gut mucosal dysfunction markers, reshape the gut microbiota [35], treatment of human Multiple schlerosis [36], Suppress liver carcinogenesis [37] Improves obesity-related inflammation and insulin resistance [38] Antidiabetic [39], α-glucosidase inhibitor [40], protect skin aging [41] Peripheral anti-nociceptive and anti-inflammation effect…”

Section: Nobilin D Ethanol/bibenzyl Derivativesmentioning

confidence: 99%

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Premna Serratifolia (PS), a member of Lamiaceae, is widely distributed in tropical and subtropical countries [1]. But in Middle Sulawesi, Indonesia, particularly in Tentena, Poso. PS is known as arogo (local name) that its leave is a cooking ingredient [2]. Arogo leave is traditionally added in high-fat cook. P. serratifolia has several synonyms, namely P. corymbosa, P. integrifolia and P. obtusifolia [3,4].Various parts of PS have health benefits. It has anti-parasitic activity against Leishmania donovani [5], anti-arthritic [6], antioxidant, and antitumor activity [7]. It is also an important nutraceutical food

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Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis

Cited by 22 publications

References 29 publications

Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability

Synthesis and biological evaluations of oleanolic acid indole derivatives as hyaluronidase inhibitors with enhanced skin permeability

Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors

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