1. Full name: Nguyễn Xuân Tứ 2. Sex: Male
3. Date of birth: November 20, 1982 4. Place of birth: Nghệ An
5. Admission decision number: Decision No. 2556/QĐ-ĐHKHTN issued on 26/7/2017 by the Rector of Hanoi University of Science.
6. Changes in academic process:
- Decision on extention No. 318/QĐ-ĐHKHTN issued on 01/02/2021 and No. 231/ QĐ-ĐHKHTN issued on 27/01/2022 by the Rector of Hanoi University of Science.
- Decision on expelling and returning the PhD student to the local authority/workplace No. 596/QĐ-ĐHKHTN issued on 02/03/2023 by the Rector of Hanoi University of Science.
7. Official thesis title: Synthesis and study of the biological activity of peptidomimetics
8. Major: Organic Chemistry 9. Code: 9440112.02
10. Supervisors:
- Main supervisor: Assoc. Prof. Dr. Mạc Đình Hùng
- Co-supervisor: Dr. Phạm Văn Phong
11. Summary of the new findings of the thesis
The thesis comprehensively and systematically studies the optimal conditions for synthesizing macrocyclic β-peptidomimetics and tests the biological activity of these compounds on MDA-MB-231 and MCF-7 breast cancer cells. Starting from natural amino acids, the thesis employed appropriate organic synthesis methods to prepare β-amino acids with good yield, and notably, the resulting products retained their chiral centers. The synthesized β-amino acids served as the starting materials for subsequent transformations to synthesize bis-N-alkylated β-peptidomimetic derivatives. The thesis investigated and optimized the condition for the Ring-Closing Metathesis (RCM) reaction of bis-N-alkylated β-peptidomimetic derivatives to form macrocyclic β-peptidomimetics, achieving good selectivity and high yield. The result was then applied to successfully synthesize 7 new macrocyclic β-peptidomimetics containing 9-membered to 13-membered rings using the RCM reaction with Grubbs-2 catalyst. As far as we are aware, no previous work has reported the synthesis of macrocyclic β-peptidomimetics containing 2 nitrogen atoms in the ring as done by this thesis.
In addition, the thesis successfully synthesized 2 new biphenyl peptidomimetic derivatives with two symmetric peptide chains at the 2,2' positions of the phenyl rings, each chain containing 3 amino acids. The single-crystal X-ray diffraction data of the two biphenyl peptidomimetics showed that both structures exhibited intramolecular hydrogen bonds and intermolecular hydrogen bonds. The single-crystal X-ray diffraction data of the two synthesized compounds not only provided information about their structures but also guided scientists in the design of peptidomimetics.
12. Practical applicability, if any:
- The thesis has completed two synthetic processes for peptidomimetic derivatives, providing a reference for chemists to use in synthesizing macrocyclic β-peptidomimetics and biphenyl peptidomimetics.
- It provides NMR, HRMS, and single-crystal X-ray diffraction data for some synthesized macrocyclic β-peptidomimetic and biphenyl peptidomimetic compounds, supporting scientific research and contributing to the training of high-quality human resources for society.
- The results of the biological activity tests on the synthesized macrocyclic β-peptidomimetic compounds showed inhibitory activity against MDA-MB-231 and MCF-7 breast cancer cells, with particularly good inhibition by compounds with 11-13-membered rings. This helps guide the search for new compounds with potential practical applications.
13. Further research directions, if any:
Optimize the structure of macrocyclic peptidomimetic compounds with 9-12-membered rings to obtain compounds with better biological activity.
14. Thesis-related publications:
[1] Lê Thúy Quỳnh, Nguyễn Xuân Tứ, Mạc Đình Hùng (2018), "Synthesis of peptide derivatives containing a biaryl scaffold", Journal of Chemistry, Vol. 56(6E1), pp. 108-111.
[2] Nguyễn Xuân Tứ, Cao Thị Thương Thương, Nguyễn Thị Xuyến, Phan Phùng Huyền Quyên, Mạc Đình Hùng (2019), "Synthesis of β-amino acids from natural amino acids", Journal of Physical, Chemical and Biological Analysis, Vol. 24 (No.3).
[3] Thuy Quynh Le, Xuan Tu Nguyen, Hung Huy Nguyen, Dinh Hung Mac, and Thai Thanh Thu Bui (2020), "Crystal structure of a tripeptide biphenyl hybrid C50H56N6O10.0.5H2O", Acta Crystallographica E76, pp. 257-260.
[4] Dinh Hieu Tran, Xuan Tu Nguyen, Thi Minh Chau Tran, Thuy Quynh Le, Chang Ho Oh, and Dinh Hung Mac (2020), "Synthesis of Macrocyclic β-Peptidomimetics by Ring-Closing Metathesis", ChemistrySelect, Vol. 5, pp. 12232–12235.
[5] Xuan Tu Nguyen, Thuy Quynh Le, Tra My Bui Thi, Dinh Hung Mac, and Thai Thanh Thu Bui (2020), "Synthesis and crystal structure of peptide dimethyl biphenyl hybrid C52H60N6O10.0.25H2O", Acta Crystallographica E76, pp. 1675-1678.
