Synthesis and Antiviral Evaluation of 1,3,5-Triazines with Aromatic Amino Acids

1. Synthesis and Antiviral Evaluation of 1,3,5-Triazines withAromatic Amino Acids

2. 1 1 Introduction conclusion 2 Chemistry 3 Antiviral Evaluation 4 SPR study Contents

3. INTRODUCTION • an effective vaccine is still far from • being available a continuous need to develop new strategies 、active principles (2) The current drug regimens need to be better tolerated and/or should reach a wider target population (3) the increasing emergence of resistance to existing drugs

4. Recently targeting ：glycans of the glycoprotein gp120 of the viral envelope. experimental results Glycans --- block the recognition of the underlying immunogenic lectins are able to inhibit HIV infection and HIV transmission by blocking virus-to-cell and cell-to-cell contact. exert activity by binding to the carbohydrates and compromising the required conformational changes

5. Prolonged exposure-- drug resistance. mutations affect the N-glycosylation sites of gp120 monkeys with mutated SIV Therefore, lectins may have a dual mechanismof action: (1) directly by binding to the glycans of the HIV envelope and thus blocking viral entry (2) indirectly triggering the immune system to recognize previously hidden immunogenic epitopes.

6. Chemistry . The proposed structures have been synthesized in a three-step strategy: (1) reaction of cyanuric chloride with the free amino groups of aminoacids to obtain monochlorotriazines. (2) nucleophilic substitution reactions with mono-, di-, or triamines to obtain monomers, dimers, or trimers, respectively. (3) saponification of the methyl esters of the amino acids to afford the desired free acids.

7. Synthesis of Monomers .

8. Synthesis of Dimers .

9. Synthesis of Trimers .

10. Synthesis of Trimers .

11. Synthesis of Trimers .

12. Antiviral Evaluation 1.Timer affordded better EC50 values gp120 2.Central core 3. 4.Trp derivatives were endowde with the most significant activities

13. SPR用途简介

14. SPR用途简介 SPR技术因其时效性，高通量，特异性及能在天然状态下研究药物分子与靶点的相互作用，为药物研发提供了有力工具。

15. Figure2. SPR analysis of the binding of compounds 8Bb (magenta), 8Cb (cyan), 12Bb (blue), 12Eb (red), 15 (green),and 18 (gold) to gp120(IIIB) injected over the surface at a fixed concentration of 12.5 μM. The biosensor chip density was 10400 RUs.

16. SPR用途简介 Figure3. SPR analysis of the binding mode of monomers, dimers and trimers of Try and Trp to HD gp120 chip at a fixed concentration of 50 μM. (a)Tyr derivatives: trimer 8Bb (blue), dimer 6Bb (red), and monomer 4bB (green). (b)Trp compounds: trimer 8Cb (blue), dimer 6Cb (red), and monomer 4Cb (green).

17. SPR用途简介 Figure 4. SPR analysis of the influence of different Ca 2+ concentrations on the binding of theTyr trimer 8Bb (on the left) and theTrp trimer 8Cb (on the right ) to HD gp120.The compounds were both at a fixed concentration of 12.5 μM. The concentrations of Ca2+ tested were:10mM (green), 2mM (blue), and 0mM (red).

18. Synthesis Future Confusion Significance Conclusions www.themegallery.com

19. Synthesis From disubstitutedchlorotriazines Monomers Trimers have good results in X4 and R5 strains. (according to SPR) Dimers Trimers The target of interactions www.themegallery.com

20. Confusion …………………… The exact locations of binding unknown whether binding with one single gp120 molecule is sufficient even between two gp120 trimers need to occur as a prerequisite for antiviral activity whether binding (cross-linking) between different gp120 molecules within the gp120 trimer www.themegallery.com

21. target Less worries metabolism effective do not need to be taken up by the target cells Not metabolized to an active species afford significant disruption of the viral infection directly binding (HIV gp120) Significance future modest ——antiviral activities potential novel HIV microbicide lead compounds www.themegallery.com

22. www.themegallery.com Thank You