Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

Sanphanya, Kingkan; Wattanapitayakul, Suvara K.; Phowichit, Suwadee; Fokin, Valery V.; Vajragupta, Opa

doi:10.1016/j.bmcl.2013.03.042

Cited by 57 publications

(43 citation statements)

References 34 publications

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“…Several series of quinolone derivatives were screened for their in vitro and in vivo antitumor activities, although almost all of them were less active than the references, the SAR was enriched .…”

Section: Antitumor Activitymentioning

confidence: 99%

Quinolone–Triazole Hybrids and their Biological Activities

Fan

Zhou

2018

Journal of Heterocyclic Chem

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Hybridization, a strategy based on the covalent fusion of two or more existing pharmacophores to create a single molecule with multiple mechanisms of action, represents an encourage approach in the development of new drugs with potential therapeutic application in several pathologies. Triazoles and quinolones occupy an important position in medicinal chemistry attribute to their various biological activities, so hybridization of these two pharmacophores may provide more effective candidates that might be able to prevent the drug resistance. This review outlines the biological activities of triazole–quinolone hybrids, and discusses their structure–activity relationship.

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Section: Antitumor Activitymentioning

confidence: 99%

Quinolone–Triazole Hybrids and their Biological Activities

Fan

Zhou

2018

Journal of Heterocyclic Chem

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“…As per literature on the docking study of known VEGFR‐2 inhibitors having common pharmacophoric features reveal the following binding interactions with VEGFR2: (i) The core structure, that is, heteroaromatic ring system interacts with the backbone NH of Cys919 residue; (ii) most inhibitors have amide or urea moieties, which interact with Glu889 and Asp1046; (iii) the other reported interactions are Glu885, Asp1046, Cys1045, Val 895, Arg1027, Phe1047, Ile1025, etc. at the active site.…”

Section: Resultsmentioning

confidence: 93%

Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole derivatives as VEGFR‐2 inhibitors

Ravula

Vamaraju

Paturi

et al. 2017

Archiv der Pharmazie

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As the blockade of the VEGFR-2 signaling pathway is a viable approach in cancer therapy, the present study focuses on a series of pyrazole based VEGFR-2 inhibitors that were designed on the basis of the hybridization approach, supported by docking and in silico computational studies. The designed compounds were synthesized through facile synthetic methods and the structures were K E Y W O R D Santiproliferative activity, molecular modeling, synthesis, VEGFR-2

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“…sorafenib. Our group has recently developed tyrosine kinase inhibitors bearing urea function and some of them exhibited antitumor activity (Sanphanya et al, 2012(Sanphanya et al, , 2013. Urea function not only does provide pharmacodynamic benefits, but it is also less metabolically labile than ester.…”

Section: Chemistrymentioning

confidence: 98%

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

et al. 2015

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Available online xxxKeywords: Caffeic acid derivatives EGFR inhibitor Triple-negative breast cancer Non-small cell lung cancer Molecular modeling Abbreviations: CA, caffeic acid CAPE, caffeic acid phenethyl ester EGFR, epidermal growth factor receptor RTK, receptor tyrosine kinase TNBC, triple-negative breast cancer a b s t r a c t A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido) vinyl)-1,2-phenylene diacetate (CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells. CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type nonsmall-cell lung cancer H460 cells with IC 50 values of 8.96 mM and 12.98 mM, respectively, these anti-proliferative effects of CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC 50 2.34 mM. The immunoblot analyses revealed that CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

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Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

Cited by 57 publications

References 34 publications

Quinolone–Triazole Hybrids and their Biological Activities

Quinolone–Triazole Hybrids and their Biological Activities

Design, synthesis, in silico and antiproliferative evaluation of novel pyrazole derivatives as VEGFR‐2 inhibitors

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

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