Virtual screening and synthesis of quinazolines as novel JAK2 inhibitors

Yang, Suhui; Khadka, Daulat Bikram; Cho, Suk Hee; Ju, Hyekyung; Lee, Kwang Youl; Han, Ho Jae; Lee, Kyung‐Tae; Cho, Won‐Jea

doi:10.1016/j.bmc.2010.11.057

Cited by 39 publications

(15 citation statements)

References 31 publications

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“…Herbal phytochemicals consist of a wide variety of biologically active chemical constituents that are ubiquitous in plants, many of which have been reported to have anti-CRC properties [11, 37, 38]. Among them, HT possesses anti-inflammatory effects and potential therapeutic properties against CRC.…”

Section: Discussionmentioning

confidence: 99%

Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from Helicteres angustifolia L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐κB and STAT3 Signaling

Gao

Dai

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Colorectal cancer (CRC) is one of the most common malignancies and most frequent cause of cancer death worldwide. The activation of both NF-κB and STAT3 signaling and the crosstalk between them play an important role in colorectal tumor. Helicteres angustifolia L. is a type of commonly used Chinese medicinal herb and possesses a wide variety of biological activities. In the present study, we investigate the effects of three triterpenes from H. angustifolia (HT) such as helicteric acid (HA), oleanic acid (OA), and betulinic acid (BA), on inhibiting CRC progression. Our results showed that HT extracts could decrease proliferation and induce apoptosis in HT-29 colorectal cancer cells. Moreover, HT extracts could suppress LPS-triggered phosphorylation of IKK, IκB, and NF-κB, attenuate IL-6-induced phosphorylation of JAK2 and STAT3, and suppress the expression of c-Myc, cyclin-D1, and BCL-xL, the downstream gene targets of NF-κB and STAT3. Therefore, HT extracts showed potent therapeutic and antitumor effects on CRC via inhibiting NF-κB and STAT3 signaling.

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Section: Discussionmentioning

confidence: 99%

Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from Helicteres angustifolia L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐κB and STAT3 Signaling

Gao

Dai

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…Other bases, including KF, Li 2 CO 3 , CsOAc, K 2 CO 3 , K 3 PO 4 , t-BuOK, LiOH, and NaOH, were less efficient ( Table 1, entries 2-10). Among the copper sources used (e.g., CuOTf, CuBr, CuCl, Cu(OTf) 2 , Cu(OAc) 2 , CuBr 2 , CuCl 2 , and CuO), CuCl exhibited the highest catalytic reactivity (91% yield, Table 1, entries [10][11][12][13][14][15][16][17]. No reaction occurred when the procedure was carried out in the absence of copper catalyst (Table 1, entry 18).…”

Section: Resultsmentioning

confidence: 99%

“…They possess a wide range of biological and pharmacological activities, including antibacterial [4], anti-inflammatory [5], antiplasmodial [6], antitumor [7], antimicrobial and antioxidant properties [8]. In addition, they have also been used as photochemotherapeutic agents [9], DNA-gyrase, JAK2, PDE5, and EGFR tyrosine kinase inhibitors [10] as well as CB2 receptor agonists [11]. Recently, Yang reported that substituted quinazolines possess novel potent and selective FLT3 inhibitory and anti-acute myeloid leukemia activities [12].…”

Section: Introductionmentioning

confidence: 99%

One-Pot Tandem Synthesis of 2-Arylquinazolines by a Multicomponent Cyclization Reaction

Zhu

et al. 2013

Molecules

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“…It is well known that MR products exhibit potent anti-inflammatory and antioxidant activities29303132. We previously identified BHPB, a tyrosine-fructose MR product as a STAT3 inhibitor, which has potential therapeutic properties against multiple diseases including RA15161718192021222333.…”

Section: Discussionmentioning

confidence: 99%

Novel synthetic (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol inhibits arthritis by targeting signal transducer and activator of transcription 3

Son

Kim

Nah

et al. 2016

Sci Rep

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Rheumatoid arthritis (RA) is a severely debilitating chronic autoimmune disease that leads to long-term joint damage. Signal transducer and activator of transcription 3 (STAT3)-targeted small molecules have shown promise as therapeutic drugs for treating RA. We previously identified (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (BHPB), a tyrosine-fructose Maillard reaction product, as a small molecule with potent anti-inflammatory and anti-arthritic properties, mediated through the inhibition of STAT3 activation. The aim of this study was to develop a novel BHPH derivative with improved anti-arthritic properties and drug-likeness. We designed and synthesised (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a novel synthetic BHPB analogue, and investigated its anti-inflammatory and anti-arthritic activities in experimentally-induced RA. We showed that MMPP strongly inhibited pro-inflammatory responses by inhibiting in vitro STAT3 activation and its downstream signalling in murine macrophages and human synoviocytes from patients with RA. Furthermore, we demonstrated that MMPP exhibited potent anti-arthritic activity in a collagen antibody-induced arthritis (CAIA) mouse model in vivo. Collectively, our results suggest that MMPP has great potential for use in the treatment of RA.

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Virtual screening and synthesis of quinazolines as novel JAK2 inhibitors

Cited by 39 publications

References 31 publications

Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from Helicteres angustifolia L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐κB and STAT3 Signaling

Helicteric Acid, Oleanic Acid, and Betulinic Acid, Three Triterpenes from Helicteres angustifolia L., Inhibit Proliferation and Induce Apoptosis in HT‐29 Colorectal Cancer Cells via Suppressing NF‐κB and STAT3 Signaling

One-Pot Tandem Synthesis of 2-Arylquinazolines by a Multicomponent Cyclization Reaction

Novel synthetic (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol inhibits arthritis by targeting signal transducer and activator of transcription 3

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