The task of the thesis: Synthesis of new derivatives of indenoisoquinoline is based on changes in B ring groups by modifying branching atoms of nitrogen atom and binding of triazole-containing hybrid compounds. Synthesis of new derivatives of indenoisoquinoline based on the change of substituents in D ring with metoxyl groups or methylendioxy. Simultaneously change the substituents on B ring through the triazole bridge by click reaction.
MINISTRY OF EDUCATION & TRAINING VIET NAM ACADEMY OF SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY OF SCIENCE AND TECHNOLOGY - - NGO HANH THUONG SYNTHESIS AND IDENTIFICATION BIOLOGICAL ACTIVITY OF SOME INDENOISOQUINOLINE DERIVATIVES Major: Organic chemistry Code: 9.44.01.14 SUMMARY OF CHEMISTRY DOCTORAL THESIS Ha Noi - 2018 This thesis was completed at: Laboratory of Medicinal Chemistry - Institute of Chemistry - Vietnam Academy of Science and Technology Scientific Supervisors: Prof Dr Nguyen Van Tuyen 1st Reviewer: 2nd Reviewer: 3rd Reviewer: The dissertation were defended at Graduate University of Science and Technology, No.18 Hoang Quoc Viet, Cau Giay District, Ha Noi City At ……………… The dissertation can be found in National Library of Vietnam and the library of Graduate University of Science and Technology A INTRODUCTION TO THESIS Graduation, scientific and practical significance of thesis topic Indenoisoquinoline has some advantages over camptothecin First, the DNA cleavage site of NSC314622 (4) is different from that of camptothecin (1), so it is possible for different cancer resistance Secondly, the indoeritol-soluble Top1-DNA complexes of indenoisoquinoline are more stable Third, the indenoisoquinoline is chemically stable Fourthly, the indenoisoquinoline was less affected by the top1-resistant mutants of R364H and N722S Two indenoisoquinolines toxic Top1: indotecan (5), indimitecan (6), were phase I clinical trials for cancer treatment and are undergoing Phase II clinical trials Figure In addition, research into hybrid compounds is gaining much interest among researchers, recent studies have shown that hybridizations can increase activity and some cases avoidance Drug resistance versus one component Thus, the synthesis of new derivatives and cytotoxic activity assays for the detection of antitoxin-active agents of Topoisomerase is of great scientific and practical significance Therefore, we chose to study "Synthesis and identification biological activity of some indenoisoquinoline derivatives" The task of the thesis Synthesis of new derivatives of indenoisoquinoline is based on changes in B ring groups by modifying branching atoms of nitrogen atom and binding of triazole-containing hybrid compounds Synthesis of new derivatives of indenoisoquinoline based on the change of substituents in D ring with metoxyl groups or methylendioxy Simultaneously change the substituents on B ring through the triazole bridge by click reaction Tested for anti-cancer activity of synthetic compounds The contribution of the thesis Successfully synthesized 41 new indenoisoquinoline compounds The estimated tumorigenic activity of 45 indenoisoquinoline compounds on two epithelial (KB) and liver (Hep-G2) cell lines, 26 of which are highly pathogenic There are 12 compounds exhibiting strong cytotoxic cytotoxic activity with IC50