Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity

Wang, Jubo; Li, Tinghan; Zhao, Tengteng; Wu, Tizhi; Liu, Chuang; Ding, Hong; Li, Zhiyu; Bian, Jinlei

doi:10.1016/j.ejmech.2019.06.024

Cited by 26 publications

(28 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, highlighted compound 14 showed significant antitumor activity in mouse acute myeloid leukaemia (AML) models without producing apparent toxic effects in vivo. Additionally, among the synthesised compounds, the piperazine and methylpiperazine substituted derivatives exhibited higher antiproliferative potency against the HepG2 cell line, while morpholine and pyrrolidine substituted analogs showed dramatically lower antiproliferative activity 39 .…”

Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Piperazine moiety is a cyclic molecule containing two nitrogen atoms in positions 1 and 4, as well as four carbon atoms. Piperazine is one of the most sought heterocyclics for the development of new drug candidates with a wide range of applications. Over 100 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antioxidant, and other activities, were reviewed. This article reviewed investigations regarding piperazine groups for the modification of natural product derivatives in the last decade, highlighting parameters that affect their biological activity.

show abstract

Section: Biological Effects Of Natural Products Containing the Piperazinyl Moietymentioning

confidence: 99%

Piperazine skeleton in the structural modification of natural products: a review

Zhang

Guo

Deng

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Wogonin directly binds to the ATP-binding pocket of CDK9 (44). One of the wogonin derivatives was also noticed to be effective against CDK9 (45).…”

Section: Regulation Of Vegf/vegfr Signalingmentioning

confidence: 99%

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review

Butt

Özbey

Malik³

et al. 2021

Cell Mol Biol (Noisy-le-grand)

View full text Add to dashboard Cite

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/β-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.

show abstract

“…The seminal discovery of flavopiridol (alvocidib) 1 (Figure . 1) whose structure was inspired by the natural antirheumatic flavonoid "Rohitukine" [19][20][21][22] led to the development of new synthetic flavonoids-based compounds as inhibitors of kinases. Alvocidib, the first CDKs (CDK1, 2,4,6,7,9) inhibitor to be tested in a clinical trial [23][24][25] is the most active CDK9 inhibitor with IC 50 value of 20 nM. This drug is capable to induce regluated cell death with a block in the cell cycle at the G1/S and G2/M phases.…”

Section: Figure 1 Flavopiridol and Mimics As Potent Cdks Inhibitorsmentioning

confidence: 99%

“…Particularly, in cancer diseases, flavonoids are known for their ability to inhibit important cell signaling proteins such as cyclin-dependent kinases (CDKs). [5][6][7] CDKs are wellknown to be the main key regulators of cell cycle progression, their hyperactivation is associated with several cancers.…”

Section: Introductionmentioning

confidence: 99%

Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency

Ibrahim

Bonnet

Brion

et al. 2020

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

In this work, unique structure of flavopiridol analogs bearing thiosugars, amino acids and heterocyclic moieties tethered to the flavopiridol via thioether and amine bonds mainly on its C ring have been prepared. The analogs bearing thioether-benzimidazoles as substituents have demonstrated high cytotoxic activity in vitro against up to seven cancer cell lines. Their cytotoxic effects are comparable to those of flavopiridol. The most active compound (13c) found after the structure-activity relationship (SAR) showed the best antiproliferative activity and was more efficient than the reference compound. In addition, compound 13c showed significant nanomolar inhibition against CDK9 and GSK3β protein kinases.

show abstract

Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity

Cited by 26 publications

References 31 publications

Piperazine skeleton in the structural modification of natural products: a review

Piperazine skeleton in the structural modification of natural products: a review

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review

Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency

Contact Info

Product

Resources

About