EVALUATION OF THE ACTIVITY NEW PIPERAZINEDIONE DERIVATIVES

Nguyen Van A1, Tran Van B2

1 Insitute of Chemistry, Vietnam Academy of Scicence and Technology (VAST)

2 Vietnam National University, Hanoi (VNU)

1.  SUMMARY

In this paper, several piperazinediones containing naphthalen moiety were synthesized as (cyclo)tryprostatin analogues by Pictet-Spengler reaction through acylation of the piperidine nitrogen, then condensation with primary amines such as n-propyl and n-butyl amine. These compounds were further treated with primary amines to afford the corresponding diketopiperazines.

Keywords: Pictet-Spengler, piperazinedione, diketopiperazines, activity, (cyclo)tryprostatin

2.  INTRODUCTION

Piperazinediones are the class of truly ubiquitous structures involved in the regulation of a wide variety of biological processes [1, 2]. The broad range of bioactivities of these molecules has led to their description as ‘privileged structures’[3,4].

3.  MATERIALS AND METHODS

3.1.  Materials

3.2.  Methods

4.  RESULTS AND DISCUSSION

Fig. 1

Table 1. Cytotoxicity evaluation

Entry / compound / IC50 (µg/mL)
KB / Hep-G2 / LU / MCF7
1 / 7a / 62.31 / >128 / >128 / >128
2 / 7b / >128 / >128 / >128 / >128
3 / 8a / 4.40 / 8.00 / 99.2 / >128
4 / 8b / >128 / >128 / >128 / >128
5 / Ellipticine / 0.625 / 0.625 / 0.625 / 0.625

Acknowledgements: This work was financially supported in part by scientific research and technological development project (code: ĐT.NCCB-ĐHUD.2011-G/07)

5.  CONCLUSIONS

6.  REFERENCES

1.  Lopez-Rodr iguez, M. L.; Ayala, D.; Benham u, B.; Morcillo, M. J.; Viso, A. Curr. (2002), Med. Chem., 9: 1867–1894.

2.  Wiesner, J.; Kettler, K.; Sakowski, J.; Ortmann, R.; Katzin, A. M.; Kimura, E. A.; Silber, K.; Klebe, G.; Jomaa, H.; Schlitzer, M. Angew. (2004) Chem., Int. Ed., 43:251–254; (f) Horton, D. A.; Bourne, G. T. Smythe, M. L. (2003) Chem. Rev. 103:893–930

3.  Cui, C-B.; Kayeka, H.; Osada, H. (1996) J. Antiobiot., 49: 832-835.

1