{"id":268,"date":"2023-02-12T02:42:04","date_gmt":"2023-02-11T18:42:04","guid":{"rendered":"https:\/\/www.yuanxustudy.cn\/?p=268"},"modified":"2023-02-12T02:59:47","modified_gmt":"2023-02-11T18:59:47","slug":"design-synthesis-and-in-vitro-evaluation-of-6-amide-2-aryl-benzoxazole-benzimidazole-derivatives-against-tumor-cells-by-inhibiting-vegfr-2-kinase","status":"publish","type":"post","link":"https:\/\/www.yuanxustudy.cn\/?p=268","title":{"rendered":"Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole\/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase"},"content":{"rendered":"<p><strong>Xu Yuan<\/strong>, Qingyi Yang, Tongyan Liu, Ke Li, Yuwen Liu, Changcheng Zhu, Zhiyun Zhang, Linghua Li, Conghai Zhang, Mingjin Xie, Jun Lin, Jihong Zhang, Yi Jin<\/p>\n<p>&nbsp;<\/p>\n<h2>Abstract<\/h2>\n<p>Herein, we have carried out a structural optimization campaign to discover the novel anti-tumor agents with our previously screened YQY-26 as the hit compound. A library of thirty-seven 6-amide-2-aryl benzoxazole\/benzimidazole derivatives has been designed and synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2 than EGFR kinases, which also displayed selective anti-proliferation potency against the HUVEC and HepG2 than the A549 and MDA-MB-231 cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis capability by chick chorioallantoic membrane (CAM) assay. Among them, compounds 9d showed the most potent anti-angiogenesis ability (79% inhibition at 10 nM\/eggs), the efficient cytotoxic activities (in vitro against the HUVEC and HepG2 cell lines with IC50 values of 1.47 and 2.57\u202f\u03bcM, respectively), and excellent VEGFR-2 kinase inhibition (IC50\u202f=\u202f0.051\u202f\u03bcM). The molecular docking analysis revealed that compound 9d is a Type II inhibitor of VEGFR-2 kinase. These results indicated that the 6-amide-2-arylbenzoxazole and 6-amide-2-aryl benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for the potential treatment of anti-angiogenesis.<\/p>\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.ejmech.2019.06.054\">\u67e5\u770b\u6587\u732e<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Herein, we have carried out a structural optimization campaign to discover the novel anti-tumor agents with our previously screened YQY-26 as the hit compound. A library of thirty-seven 6-amide-2-aryl benzoxazole\/benzimidazole derivatives has been designed and synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2 than EGFR kinases, which also displayed selective anti-proliferation potency against the HUVEC and HepG2 than the A549 and MDA-MB-231 cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis capability by chick chorioallantoic membrane (CAM) assay. Among them, compounds 9d showed the most potent anti-angiogenesis ability (79% inhibition at 10 nM\/eggs), the efficient cytotoxic activities (in vitro against the HUVEC and HepG2 cell lines with IC50 values of 1.47 and 2.57\u202f\u03bcM, respectively), and excellent VEGFR-2 kinase inhibition (IC50\u202f=\u202f0.051\u202f\u03bcM). The molecular docking analysis revealed that compound 9d is a Type II inhibitor of VEGFR-2 kinase. These results indicated that the 6-amide-2-arylbenzoxazole and 6-amide-2-aryl benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for the potential treatment of anti-angiogenesis.<br \/>\n<a href=\"https:\/\/doi.org\/10.1016\/j.ejmech.2019.06.054\">\u67e5\u770b\u6587\u732e<\/a><\/p>\n","protected":false},"author":1,"featured_media":127,"comment_status":"closed","ping_status":"closed","sticky":true,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"default","ast-global-header-display":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","footnotes":""},"categories":[9],"tags":[11],"class_list":["post-268","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-art","tag-11"],"_links":{"self":[{"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/posts\/268","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=268"}],"version-history":[{"count":3,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/posts\/268\/revisions"}],"predecessor-version":[{"id":285,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/posts\/268\/revisions\/285"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=\/wp\/v2\/media\/127"}],"wp:attachment":[{"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=268"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=268"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.yuanxustudy.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=268"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}