Summary of Chemisttry doctoral thesis: Research on the synthesis of hybrid compounds of some triterpenoids containing benzamide and hydroxamate groups

Study on synthesis of hybrid compounds of some triterpenoids containing benzamide and hydroxamate groups in order to search for hybrid compounds with high biological activity, as a scientific basis for further research to create anti-cancer drugs, contribute to health care for the community.
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Summary of Chemisttry doctoral thesis: Research on the synthesis of hybrid compounds of some triterpenoids containing benzamide and hydroxamate groups MINISTRY OF EDUCATION VIETNAM ACADEMY OF AND TRAINING SCIENCE AND TECHNOLOGY GRADUATE UNIVERSITY SCIENCE AND TECHNOLOGY ------------------ DINH THI CUC SUMMARY OF CHEMISTTRY DOCTORAL THESIS STUDY ON SYNTHESIS OF HYBRID COMPOUNDS OF SOME TRITERPENOIDS CONTAINING BENZAMIDE AND HYDROXAMATE GROUPS Major : Organic chemistry Code: 9.44.01.14 Hanoi-2020 The thesis was completed in Graduate University Science and Technology, Vietnam Academy of Science and Technology.  Supervisor: Prof.Dr. Nguyen Van Tuyen Dr. Le Nhat Thuy Giang Reviewer 1: Reviewer 2: Reviewer 3: The thesis will be presented before the Council for Evaluation of Ph.D. thesis at the Academy, meeting at Graduate University Science and Technology, Vietnam Academy of Science at …. am, ….March, , 2020. A. INTRODUCTION OF THE THESIS 1. The urgency, scientific and practical significance of the thesis topic. Cancer is one of the most threatening diseases in the world. Globally an estimated 8.2 million people died from cancer in 2012, and lung cancer (bronchial and tracheal cancer) increased significantly has become the fifth leading cause of death in 2012, killing 1.1 million men and 0.5 million women. Currently, hybrid structured drugs are increasingly being studied and synthesized by scientists to create hybrid compounds with high biological activity that are superior to the original ones. Combining biologically active components to create new structures with exciting activities is currently a research direction that attracts the attention of many scientists. Triterpenoids are a group of natural compounds or their derivatives that have received significant research interest from scientists in recent years. Many tritecpenoid compounds such as betulin, betulinic acid, ursolic acid, oleanolic acid have been declared to have anti-HIV, antibacterial, antifungal, anti-inflammatory and anti-cancer activity. Besides, benzamide compounds such as MS-275, MGCD- 0103 are interesting bioactive compounds, has been approved by the US Food and Drug Administration (US-FDA) for the treatment of solid organs, leukemia, and metastatic melanoma of late stage [7-11]. Hydroxamic compounds such as vorinostat, also known as zolinza (SAHA) were also approved by the FDA in 2006 for the treatment of T-cell skin lymphoma, trichosatin A (TSA) and belinostat (PXD-101) for therapeutic use. donation and blood cancer, panobinostat (LBH- 589) in the treatment of solid organs, AML, ALL, MDS [12-16]. However, hybrid compounds of triterpenoid containing benzamide and hydroxamate groups have not been studied much. The research on the synthesis of triterpenoid hybrid compounds 1 containing benzamide group, hydroxamate group and testing of cytotoxic activity to search for compounds with anticancer activity is a new research direction. Based on such ideas, we chose the topic: Research on the synthesis of hybrid compounds of some triterpenoids containing benzamide and hydroxamate groups is a new, interesting and highly practical scientific matter. 2.Thesis objectives Study on synthesis of hybrid compounds of some triterpenoids containing benzamide and hydroxamate groups in order to search for hybrid compounds with high biological activity, as a scientific basis for further research to create anti-cancer drugs, contribute to health care for the community. 3. The new contribution of this thesis 1. For the first time successfully designed and synthesized 13 new compounds of some triterpenoids containing benzamide group and 16 new compounds of some triterpenoids containing hydroxamate group by ester and amide bridge. 2. Has synthesized 3 new amide derivatives 91, 93, 95, has not been published in any documents. 3. A method of improving the synthesis of benzamide and hydroxamate derivatives by BOP activating agent instead of using the old activating agent is DCC or CDI, thereby opening a new direction to effectively synthesize these compounds. 4. Has confirmed the structure of new compounds from the results of spectral data analysis: IR, 1H-NMR, 13C-NMR and LC-MS/MS. 5. For the first time, assessing the cytotoxic activity of 29 new compounds on 2 cancer cell lines in humans, cell KB (Human epidemic carcinoma) and cell Hep-G2 (Hepatocellular carcinoma), inside, there are 5 new compounds 89c, 89e, 89f, 92a, 96b has strong cytotoxic activity with IC50 values < 10 µM. 2 4. The layout of the thesis The thesis has 127 pages including: Introduction 2 pages Chapter 1: Overview, 25 pages Chapter 2: Experiment, 35 pages Chapter 3: Results and discussion, 61 pages Conclusions: 1 page. References: include 100 references relating to close area research of thesis, updated until 2018. Appendix: 51 pages, including all the spectra of the synthesized compounds. 5. Research methods Substances synthesized by known modern organic synthesis methods, are modified and applied appropriately in specific cases. The reaction product is cleaned by column chromatography. The structure of the product is determined by modern spectroscopic methods such as: IR, 1H-NMR, 13C-NMR, LC-MS/MS. Biological activity was assessed by Mossman's method on two cancer cell lines in humans, KB and Hep-G2. B- THE THESIS CONTENT Chapter 1. OVERVIEW The overview of the thesis consists of 25 pages with the following main contents: - Triterpenoid derivatives and their biological activity. - Synthesis and biolog ...