Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent

Wu, Panpan; Zheng, Jie; Huang, Tianyi; Li, Dianmeng; Hu, Qingqing; Cheng, AnMing; Jiang, Zhengyun; Jiao, Luoying; Zhao, Suqing; Zhang, Kun

doi:10.1371/journal.pone.0138767

Cited by 19 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the previous studies, we can highlight the excellent value of accuracy obtained by Gomez-Jeria et al (Gómez-Jeria & Gazzano, 2016) and Wu et al (Wu et al, 2015) higher than 95%, but with a very limited data on the amount of compounds. Jabeen et al (2014) and Saqib et al (Saqib & Siddiqi, 2009) with 42 compounds obtained values around 94% with the PLS technique.…”

Section: Comparison To Other Approachesmentioning

confidence: 56%

See 1 more Smart Citation

Beyond model interpretability using LDA and decision trees for α‐amylase and α‐glucosidase inhibitor classification studies

et al. 2019

View full text Add to dashboard Cite

In this report are used two data sets involving the main antidiabetic enzyme targets α‐amylase and α‐glucosidase. The prediction of α‐amylase and α‐glucosidase inhibitory activity as antidiabetic is carried out using LDA and classification trees (CT). A large data set of 640 compounds for α‐amylase and 1546 compounds in the case of α‐glucosidase are selected to develop the tree model. In the case of CT‐J48 have the better classification model performances for both targets with values above 80%–90% for the training and prediction sets, correspondingly. The best model shows an accuracy higher than 95% for training set; the model was also validated using 10‐fold cross‐validation procedure and through a test set achieving accuracy values of 85.32% and 86.80%, correspondingly. Additionally, the obtained model is compared with other approaches previously published in the international literature showing better results. Finally, we can say that the present results provided a double‐target approach for increasing the estimation of antidiabetic chemicals identification aimed by double‐way workflow in virtual screening pipelines.

show abstract

Section: Comparison To Other Approachesmentioning

confidence: 56%

“…(Gómez‐Jeria & Gazzano, ) and Wu et al. (Wu et al., ) higher than 95%, but with a very limited data on the amount of compounds. Jabeen et al.…”

Section: Resultsmentioning

confidence: 98%

Beyond model interpretability using LDA and decision trees for α‐amylase and α‐glucosidase inhibitor classification studies

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This might be on account of the size of the active site of the target protein. Moreover, the α-glucosidase inhibition activity was more than doubled while the hydroxyl group of UA was oxidized into ketone (UA-O, IC 50 = 2.47 ± 0.14 μM)27. And analogues from UA-O-a to UA-O-j were obtained based on this ketone.…”

Section: Resultsmentioning

confidence: 99%

“…Based on our previous studies, UA and some of its analogues have significant inhibitory activity to α-glucosidase, which might play an important role for treatment of DM and its complications2627. In this study, two series of UA analogues have been described and synthesized.…”

mentioning

confidence: 99%

Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors

Zhang

Cui

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50 values of 0.71 ± 0.27 μM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.

show abstract

“…Lastly, the 3-oxo anlogue (78) was developed through oxidation with pyridinium chlorochromate. All the structure of these UA derivatives were elucidated by a series of spectroscopic techniques, such as nuclear magnetic resonance (NMR) including 13 C-NMR and 1 H-NMR with melting point, high resolution mass spectrometry, and electrospray ionization mass spectrometry (ESI-MS) [67].…”

Section: Chemistry Of Uamentioning

confidence: 99%

Ursolic Acid and Its Derivatives as Bioactive Agents

et al. 2019

View full text Add to dashboard Cite

Non-communicable diseases (NCDs) such as cancer, diabetes, and chronic respiratory and cardiovascular diseases continue to be threatening and deadly to human kind. Resistance to and side effects of known drugs for treatment further increase the threat, while at the same time leaving scientists to search for alternative sources from nature, especially from plants. Pentacyclic triterpenoids (PT) from medicinal plants have been identified as one class of secondary metabolites that could play a critical role in the treatment and management of several NCDs. One of such PT is ursolic acid (UA, 3 β-hydroxy-urs-12-en-28-oic acid), which possesses important biological effects, including anti-inflammatory, anticancer, antidiabetic, antioxidant and antibacterial effects, but its bioavailability and solubility limits its clinical application. Mimusops caffra, Ilex paraguarieni, and Glechoma hederacea, have been reported as major sources of UA. The chemistry of UA has been studied extensively based on the literature, with modifications mostly having been made at positions C-3 (hydroxyl), C12-C13 (double bonds) and C-28 (carboxylic acid), leading to several UA derivatives (esters, amides, oxadiazole quinolone, etc.) with enhanced potency, bioavailability and water solubility. This article comprehensively reviews the information that has become available over the last decade with respect to the sources, chemistry, biological potency and clinical trials of UA and its derivatives as potential therapeutic agents, with a focus on addressing NCDs.

show abstract

Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent

Cited by 19 publications

References 34 publications

Beyond model interpretability using LDA and decision trees for α‐amylase and α‐glucosidase inhibitor classification studies

Beyond model interpretability using LDA and decision trees for α‐amylase and α‐glucosidase inhibitor classification studies

Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors

Ursolic Acid and Its Derivatives as Bioactive Agents

Contact Info

Product

Resources

About