{"id":6984,"date":"2017-02-07T15:50:57","date_gmt":"2017-02-07T12:50:57","guid":{"rendered":"http:\/\/3alamaltanmya.com\/?p=6984"},"modified":"2017-02-07T15:50:57","modified_gmt":"2017-02-07T12:50:57","slug":"raed-m-maklad-omar-m-aly-el-shimaa-m-n-abdelhafez-dalia-sayed-aea-scholars","status":"publish","type":"post","link":"https:\/\/3alamaltanmya.com\/?p=6984","title":{"rendered":"Raed M.Maklad , Omar M. Aly  ; El-Shimaa M. N. AbdelHafez ; Dalia A. Sayed. (AEA-Scholars)"},"content":{"rendered":"<p style=\"direction: ltr; text-align: center;\"><strong>Raed M.Maklad , Omar M. Aly ; El-Shimaa M. N. AbdelHafez ; Dalia A. Sayed.\u00a0<\/strong><\/p>\n<p style=\"direction: ltr; text-align: center;\">Association of Egyptian-American Scholars<\/p>\n<p style=\"direction: ltr;\"><strong><u>Introduction: <\/u><\/strong><\/p>\n<p style=\"direction: ltr;\">Although most colchicine-building-site inhibitors reversibly bind to the tubulin, design and synthesis of irreversible inhibitors may lead to dramatic increase of anticancer activity. The technique involves covalent bon-formation with tubulin-receptor-pocket by alkylation of its nucleophilic aminoacid. moieties&#8221;e.g.terminal-NH2(Lysine)&amp;SH-group(Cysteine)&#8221;using electrophilic ligands.Alkylatingys239caused cessation of tubullin- polymerization.<\/p>\n<p style=\"direction: ltr;\"><strong><u>Scope:<\/u><\/strong><\/p>\n<p style=\"direction: ltr;\">-computer-aided screening of three series of potential antitubulin<\/p>\n<p style=\"direction: ltr;\">agents(diacylhydrazines<strong>9a- c<\/strong>,bis-hydrazonoylchlorides<strong>10a-c <\/strong>and triazoles<strong>13a-b<\/strong>)via docking-study inside colchicine- binding-site of tubulin<\/p>\n<p style=\"direction: ltr;\">-Synthesis of analogues with the best binding-interactions <strong>(schemes1&amp;2)<\/strong><\/p>\n<p style=\"direction: ltr;\">maintaining essential-3,4,5-trimethoxyphenyl(ring A)with different<\/p>\n<p style=\"direction: ltr;\">ringB-substitutions sometimes with alkylating linker (CI)C=NC(CI) as in bis-hydrazonoylchlorides<strong>10a-c<\/strong><\/p>\n<p style=\"direction: ltr;\">-Structure confirmation byIR, HNMR,DEPT-Q\u00a0 C NMR.MS&amp;elemental analysis.<\/p>\n<p style=\"direction: ltr;\">-3D-structure-elucidation of some bis-hydrazonoylchlorides (stereochemistry of-C=N) using single-crystal X-ray-crystallallography.<\/p>\n<p style=\"direction: ltr;\">-Screening of in-vitro anticancer &amp;antitubulin activities of target compounds to prove their mechanism of action.<\/p>\n<p style=\"direction: ltr;\"><strong><u>Conclusion:<\/u><\/strong><\/p>\n<p style=\"direction: ltr;\">&#8211; Diacylhydrazines <strong>9a-c <\/strong>and triaryltriazoles<strong>13a-b<\/strong> are moderately cytotoxic against several cancer-cell lines.<\/p>\n<p style=\"direction: ltr;\">&#8211; All tested bis-hydrazonoylchorides <strong>10a, 10b1, 10b2 <\/strong>and <strong>10c<\/strong> revealed potent antiproliferative activities against NCI-H522cell-line in the nano-molar-scale.<\/p>\n<p style=\"direction: ltr;\">&#8211; The most potent derivative <strong>10b2<\/strong> has broken the record ofCA-4indicating the role of both3- OAc and OCH3substituents at ringB<\/p>\n<p style=\"direction: ltr;\">&#8211; Tubulin inhibitory activity was proven as the mechanism-of-action of bis-hydrazonoylchlorides; irreversible inhibition is suggested(especially alkylation by C(CI)=N group,<strong>Scheme.3<\/strong>).<\/p>\n<p style=\"direction: ltr;\">&#8211; <strong>10c <\/strong>(having-3-OH,4-OMe-substitution)is still less-active than <strong>10b2<\/strong> indicating that 3- acetoxy group exerts good interaction with the receptor.<\/p>\n<p style=\"direction: ltr;\">&#8211; Stereochemistry at-C=N-affects the appropriate orientation of<\/p>\n<p style=\"direction: ltr;\">bis-hydrazonoylchlorides inside receptor which dramatically affects their anticancer activities,as shown by different cytotoxicities and tubulin-inhibitory-activities of both geometrical isomers<strong>10b1<\/strong> and<strong> 10b2.<\/strong><\/p>\n<p style=\"direction: ltr;\">&#8211; Further investigation of bis-hydrazonoylchlorides is recommended for optimization of theirSAR-study and proving their tubulin-alkylation mechanism.<\/p>\n<p style=\"direction: ltr;\">This article was published in <a href=\"http:\/\/3alamaltanmya.com\/\">3alamaltanmya<\/a><\/p>\n<p style=\"direction: ltr;\">sponsored by <a href=\"http:\/\/www.mahafouad.net\/%D8%B9%D9%86-%D8%A7%D9%84%D8%A7%D9%83%D8%A7%D8%AF%D9%8A%D9%85%D9%8A%D9%87\">Future Builders International Academy<\/a><\/p>\n<p style=\"direction: ltr;\">Led by <a href=\"http:\/\/www.mahafouad.net\/%d8%b9%d9%86-%d8%af-%d9%85%d9%87%d8%a7-%d9%81%d8%a4%d8%a7%d8%af\/\">Dr.Maha Fouad<\/a><\/p>\n<p><img decoding=\"async\" class=\"tie-appear alignleft\" style=\"direction: ltr;\" src=\"http:\/\/3alamaltanmya.com\/wp-content\/uploads\/e5f2ef68-75e1-4678-9ffc-3479da505483-300x177.jpg\" alt=\"e5f2ef68-75e1-4678-9ffc-3479da505483\" \/><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Raed M.Maklad , Omar M. Aly ; El-Shimaa M. N. AbdelHafez ; Dalia A. Sayed.\u00a0 Association of Egyptian-American Scholars Introduction: Although most colchicine-building-site inhibitors reversibly bind to the tubulin, design and synthesis of irreversible inhibitors may lead to dramatic increase of anticancer activity. The technique involves covalent bon-formation with tubulin-receptor-pocket by alkylation of its nucleophilic &hellip;<\/p>\n","protected":false},"author":1,"featured_media":6990,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11953],"tags":[14523,14726,14727,14527,14529,14728],"class_list":["post-6984","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-11953","tag-3alamaltanmya","tag-colchicine","tag-diacylhydrazines","tag-fbia","tag-future-builders-international-academy","tag-tubullin-polymerization"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.4 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Raed M.Maklad , Omar M. Aly ; El-Shimaa M. N. AbdelHafez ; Dalia A. Sayed. (AEA-Scholars) - \u062c\u0631\u064a\u062f\u0629 \u0639\u0627\u0644\u0645 \u0627\u0644\u062a\u0646\u0645\u064a\u0629<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/3alamaltanmya.com\/?p=6984\" class=\"yoast-seo-meta-tag\" \/>\n<meta property=\"og:locale\" content=\"ar_AR\" class=\"yoast-seo-meta-tag\" \/>\n<meta property=\"og:type\" content=\"article\" class=\"yoast-seo-meta-tag\" \/>\n<meta property=\"og:title\" content=\"Raed M.Maklad , Omar M. Aly ; El-Shimaa M. N. AbdelHafez ; Dalia A. Sayed. (AEA-Scholars) - \u062c\u0631\u064a\u062f\u0629 \u0639\u0627\u0644\u0645 \u0627\u0644\u062a\u0646\u0645\u064a\u0629\" class=\"yoast-seo-meta-tag\" \/>\n<meta property=\"og:description\" content=\"Raed M.Maklad , Omar M. Aly ; El-Shimaa M. N. AbdelHafez ; Dalia A. 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