Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors

Dang, Zhao; Zhu, Li; Wei, Lai; Bogerd, Hal P.; Lee, Kuo‐Hsiung; Huang, Li; Chen, Chin-Ho

doi:10.1021/acsmedchemlett.5b00339

Cited by 64 publications

(64 citation statements)

References 31 publications

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“…This property may be achievable by examining other natural aloperine derivatives from Sophora species and others, or synthetic derivatives that have already been reported (72). In the wider sense, aloperine also interacts with other, nonchannel proteins (72), which may also be beneficial clinically, but could possibly limit its usefulness as a pharmacological tool in determining precise physiological roles of KCNQ5 in vivo.…”

Section: Discussionmentioning

confidence: 99%

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Manville

Horst

Redford

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.

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Section: Discussionmentioning

confidence: 99%

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Manville

Horst

Redford

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The anti‐HIV activity of the compounds against the MT4 cells were measured as described previously . HIV‐1 replication assay was established by MT4 Cells plated in 96‐well plates.…”

Section: Methodsmentioning

confidence: 99%

Terpenes from Euphorbia antiquorum and Their in Vitro Anti‐HIV Activity

Dong

Chen

et al. 2018

Chemistry & Biodiversity

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Three new compounds (1 - 3), including two euphane type triterpenes, 24,24-dimethoxy-25,26,27-trinoreuphan-3β-ol (1) and (24S)-24-hydroperoxyeupha-8,25-dien-3β-ol (2), and an ent-atisine diterpene, ent-atisane-3α,16α,17-triol (3), were isolated from an acetone extract of the stems of Euphorbia antiquorum, together with eight known diterpenes (4 - 11). The structures of compounds (1 - 11) were elucidated using NMR and MS spectroscopic methods. Compound 7 showed moderate activity against HIV-1 replication in vitro (EC = 1.38 μm).

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“…Anti‐HIV‐1 assay was performed according to a feasible and reliable method developed by Chen . AZT ( Sigma–Aldrich , purity >98 %) was used as positive control.…”

Section: Methodsmentioning

confidence: 99%

Diterpenoids from Euphorbia neriifolia and Their Related Anti‐HIV and Cytotoxic Activity

Feng

Liú

et al. 2019

Chemistry & Biodiversity

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Fifteen diterpenoids (1 -15), including three undescribed ones with ent-atisane skeleton, eupnerias G -I (1 -3), were obtained from Euphorbia neriifolia. Compounds 1-3 were established through comprehensive spectroscopic analysis. Compounds 4 and 5 exhibited obvious anti-HIV-1 effect, and their EC 50 were 6.6 � 3.2 and 6.4 � 2.5 μg mL À 1 , respectively. Compound 6 exhibited moderate cytotoxicity on HepG2 and HepG2/Adr cells with IC 50 at 13.70 and 15.57 μM, respectively. In addition, compound 15 exhibited significant cytotoxicity on HepG2 cell lines (IC 50 = 0.01 μM), while it did not show any cytotoxicity against HepG2/Adr cell lines.

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Aloperine and Its Derivatives as a New Class of HIV-1 Entry Inhibitors

Cited by 64 publications

References 31 publications

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Terpenes from Euphorbia antiquorum and Their in Vitro Anti‐HIV Activity

Diterpenoids from Euphorbia neriifolia and Their Related Anti‐HIV and Cytotoxic Activity

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