Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

Cao, Jiyue; Ma, Chunhua; Zang, Jie; Gao, Shuai; Gao, Qianwen; Kong, Xiujie; Yan, Yizhou; Liang, Xuewu; Ding, Qin'ge; Zhao, Cui; Wang, Binghe; Xu, Wenfang; Zhang, Yingjie

doi:10.1016/j.bmc.2018.04.041

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…5) displayed more augmented cellular activity than the conforming salt did, with a nearly 10-fold improvement in potency. Cao et al 67 reported that leucine-ureido-triazole conjugates were synthesised as aminopeptidase N inhibitors using the 'click reaction'. In their study, compound 24 ( Fig.…”

Section: 23-triazole-linked Peptide Type Compoundsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: 23-triazole-linked Peptide Type Compoundsmentioning

confidence: 99%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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“…1). 23–30 Zhao and Aisa identified a series of triazole‐derivatives with considerable profile against influenza B virus 31 . He et al .…”

Section: Introductionmentioning

confidence: 99%

“…1). [23][24][25][26][27][28][29][30] Zhao and Aisa identified a series of triazolederivatives with considerable profile against influenza B virus. 31 He et al found triazole derivatives possessed potent bioactivity as antiviral inhibitors of H1N1 influenza virus.…”

Section: Introductionmentioning

confidence: 99%

Discovery of phosphonate derivatives containing different substituted 1,2,3‐triazole motif as promising tobacco mosaic virus (TMV) helicase inhibitors for controlling plant viral diseases

Liu

Yang

Ding

et al. 2023

Pest Management Science

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BackgroundThe discovery and identification of targets is of far‐reaching significance for developing novel pesticide candidates and increasing the probability of success. To explore and identify highly effective tobacco mosaic virus (TMV) helicase‐targeted lead structures, a series of novel phosphonate derivatives containing a 1,2,3‐triazole motif were rationally engineered and their antiviral activity was assessed.ResultsBioassay results showed that the optimized B17 exhibited more potent curative activity (EC50 = 271.5 μg mL−1) against TMV in vivo, which was superior to that of commercial Ribavirin (EC50 = 689.3 μg mL−1). B17 presented a stronger binding capacity through binding analysis with helicase, affording a corresponding value of 12.7 μM. Enzyme activity assay showed B17 exhibited excellent inhibitory activity on TMV helicase (39.2% at 300 μM). Furthermore, molecular docking simulations demonstrated that B17 displayed strong hydrogen‐bond interactions (2.1, 2.1, 2.2, and 3.2 Å) with Ala‐33, Gly‐10, Gly‐8, and Glu‐217 of TMV helicase. Encouragingly, transmission electron microscopy analysis revealed that B17 could remarkably disrupt surface morphology and inhibit TMV proliferation. Additionally, these compounds also displayed potential anti‐CMV (cucumber mosaic virus) and antipathogens (Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri) by expanding their applications in agriculture.ConclusionCurrent research demonstrated that B17 could be considered as a potential antiviral agent alternative though targeting TMV helicase. © 2023 Society of Chemical Industry.

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“…Our previous structure−activity relationship (SAR) study showed that isobutyl was a privileged group for the S1' pocket and the S1 pocket could accommodate various larger aromatic groups. 33 According to the above structure analysis, compound BA was designed by hybridization of the key pharmacophores of AZD5363 and bestatin (Figure 1). Considering that hydroxamic acid is a more potent Zn 2+ binding group, the carboxylic acid group of hybrid BA was replaced with hydroxamic acid, leading to target compounds 5c and 5h.…”

mentioning

confidence: 99%

“…The binding mode of bestatin in hAPN (PDB Code: 4FYR, Figure ) revealed that the carboxylate group of bestatin bidentately coordinated the catalytic Zn 2+ of APN, with the terminal isobutyl and phenyl groups occupying the S1’ and S1 pockets, respectively. Our previous structure–activity relationship (SAR) study showed that isobutyl was a privileged group for the S1’ pocket and the S1 pocket could accommodate various larger aromatic groups …”

mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of APN and AKT Dual-Target Inhibitors

Liu

Dong

Zhao

et al. 2021

ACS Med. Chem. Lett.

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Herein a novel series of APN and AKT dual inhibitors were derived from the clinical AKT inhibitor AZD5363. It was demonstrated that most compounds exhibited remarkable APN inhibitory activities with the most potent compound 8b (IC50 = 0.05 ± 0.01 μM) being over 70-fold more potent than the approved APN inhibitor bestatin (IC50 = 3.64 ± 0.56 μM). The moderate AKT inhibitory potencies of target compounds were also confirmed, with 5f and 5h possessing AKT1 IC50 values of 0.12 and 0.27 μM, respectively. More importantly, the APN IC50 values of 5f and 5h were 0.96 and 0.21 μM, respectively, indicating their balanced APN and AKT dual inhibition. HUVEC tube formation assays confirmed the superior APN inhibitory activities of 5f and 5h relative to bestatin at the cellular level. Western blot analysis demonstrated that 5h could effectively inhibit the phosphorylation of GSK3β, the intracellular substrate of AKT.

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Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

Cited by 11 publications

References 27 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Discovery of phosphonate derivatives containing different substituted 1,2,3‐triazole motif as promising tobacco mosaic virus (TMV) helicase inhibitors for controlling plant viral diseases

Design, Synthesis, and Biological Evaluation of APN and AKT Dual-Target Inhibitors

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