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Molecules 2016, 21(6), 771; doi:10.3390/molecules21060771

Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition

1
College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
2
RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA
3
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 31 March 2016 / Revised: 24 May 2016 / Accepted: 8 June 2016 / Published: 20 June 2016
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Abstract

A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 μM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 μM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility. View Full-Text
Keywords: allopurinol derivatives; cytotoxicity; human hepatoma carcinoma cell; XOD inhibition allopurinol derivatives; cytotoxicity; human hepatoma carcinoma cell; XOD inhibition
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Li, Y.; Cao, T.-T.; Guo, S.; Zhong, Q.; Li, C.-H.; Li, Y.; Dong, L.; Zheng, S.; Wang, G.; Yin, S.-F. Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition. Molecules 2016, 21, 771.

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