Preliminary in vitro biological evaluation of novel O6-benzylguanine derivative-precursors of PET tracers for the DNA repair protein AGT

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Preliminary in vitro biological evaluation of novel O⁶-benzylguanine derivative-precursors of PET tracers for the DNA repair protein AGT

Wei-Wei He, Zhao-Fei Liu, Dan Liu, Bing Jia, Fan Wang^*, Yu-Xin Cui^**

1. The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China;
2.Medical Isotope Research Center, Peking University, Beijing 100083, China;
3.Medical and Healthy Analysis Center, Peking University, Beijing 100083, China

Received:2007-10-08 Revised:2008-01-10 Online:2008-03-15 Published:2008-03-15
Contact: Fan Wang*, Yu-Xin Cui**

Abstract

Abstract:

A series of O6-benzylguanine (O6-BG) derivatives was synthesized, and their in vitro AGT (O6-Alkylguanine DNA alkyltransferase) inhibitory ability was evaluated by MTT method to investigate the possibility to be promising precursors of PET tracers. O6-BG and its derivatives, HMBG, MOBG, MOMBG, BABP and PEG, were synthesized from guanine respectively. The AGT inhibitory ability of the compounds were tested by evaluating their effects on increasing sensitivity of HeLa cancer cells to 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) with MTT method. Their order of AGT inhibitory activities follows HMBG≥O6-BG≥MOBG≥MOMBG, whereas the BABP and PEG showed no AGT inhibition activity. HMBG, MOBG and MOMBG would be promising as precursor candidates of PET tracers for tumor imaging.

Key words: O6-Benzylguanine derivatives, O6-Benzylguanine derivatives, O6-Alkylguanine DNA alkyltransferase, O6-Alkylguanine DNA alkyltransferase, MTT, MTT, Positron emission tomography, Positron emission tomography

CLC Number:

R916.41

Supporting:

Wei-Wei He, Zhao-Fei Liu, Dan Liu, Bing Jia, Fan Wang^*, Yu-Xin Cui^**. Preliminary in vitro biological evaluation of novel O⁶-benzylguanine derivative-precursors of PET tracers for the DNA repair protein AGT[J]. .

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Preliminary in vitro biological evaluation of novel O⁶-benzylguanine derivative-precursors of PET tracers for the DNA repair protein AGT

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