{"id":562,"date":"2024-04-29T01:32:33","date_gmt":"2024-04-29T01:32:33","guid":{"rendered":"https:\/\/src.cikeys.com\/2024\/?page_id=562"},"modified":"2024-04-29T01:32:33","modified_gmt":"2024-04-29T01:32:33","slug":"synthesis-biological-evaluation-and-structure-activity-relationship-of-diversified-c-4-analogs-of-podophyllotoxin-as-tubulin-inhibitors","status":"publish","type":"page","link":"https:\/\/src.cikeys.com\/2024\/conference-schedule\/poster-presentations\/poster-presentations-session-3\/synthesis-biological-evaluation-and-structure-activity-relationship-of-diversified-c-4-analogs-of-podophyllotoxin-as-tubulin-inhibitors\/","title":{"rendered":"Synthesis, Biological Evaluation, and Structure-Activity Relationship of Diversified C-4 Analogs of Podophyllotoxin as Tubulin Inhibitors"},"content":{"rendered":"\n

Grace Yu, & Dr. Edward Njoo<\/h2>\n\n\n\n
\n
\n

The rich diversity of lignin small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of several FDA-approved anticancer agents, including DNA topoisomerase inhibitors etoposide and teniposide. While these compounds share the same tetracyclic core, two subtle structural changes that differentiate podophyllotoxin from its DNA topoisomerase-binding analogs\u2014the presence of 4\u2019 methylation on the aromatic ring and stereospecific glycosylation at the C-4 hydroxyl\u2014yield two independent mechanisms. Given the immense pharmacological importance of these two features, we sought to establish a structure-activity relationship regarding modification at C-4 on the potency, specificity, and chemical properties of podophyllotoxin. Here, we synthesized a systematic library of 24 podophyllotoxin analogs with analogous ester, carbonate, and carbamate substitutions. The antiproliferative activity and efficacy of our analogs as tubulin inhibitors was evaluated through cell viability assays, tubulin polymerization assays, computer docking models, and cell cycle analysis. Our previous efforts with esters showed that increasing C-4 bulk decreases potency against human cancer cells but insignificantly impacts cell-free assays. From our preliminary SAR, small carbocyclic carbamates at C-4 are well tolerated in cell free tubulin polymerization experiments, but large, bulky alkyl groups are less tolerated.<\/p>\n<\/div>\n\n\n\n

\n

Poster Presentation<\/strong><\/a><\/p>\n\n\n\n

Session 3<\/a><\/p>\n\n\n\n

2:45pm \u2013<\/strong> 4:00pm
Grand Salon<\/p>\n\n\n\n

Chemistry<\/strong><\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Grace Yu, & Dr. Edward Njoo The rich diversity of lignin small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of several FDA-approved anticancer agents, including DNA topoisomerase inhibitors etoposide and teniposide. While these compounds share the same tetracyclic core, two subtle structural changes […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":48,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"categories":[5,8],"tags":[29],"class_list":["post-562","page","type-page","status-publish","hentry","category-poster-presentations","category-session-3","tag-chemistry","post"],"_links":{"self":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/562","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/comments?post=562"}],"version-history":[{"count":1,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/562\/revisions"}],"predecessor-version":[{"id":655,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/562\/revisions\/655"}],"up":[{"embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/pages\/48"}],"wp:attachment":[{"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/media?parent=562"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/categories?post=562"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/src.cikeys.com\/2024\/wp-json\/wp\/v2\/tags?post=562"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}