Synthesis, Anticancer Activity and UPLC Analysis of the Stability of Some New Benzimidazole-4,7-dione Derivatives

Molecules

Katarzyna Bᐪszczak-Świątkiewicz¹  Diogo Correia Almeida²  Maria De Jesus Perry² 

[1] Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Muszyńskiego 1, Łódź 90-151, Poland; E-Mail:;Department of Pharmaceutical Chemistry and Therapeutics, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, Lisboa 1649-003, Portugal; E-Mails:

关键词: anticancer prodrug;    hypoxia;    benzimidazole-4;    7-dione;    N-oxide benzimidazole-4;    7-dione;    UPLC;   

DOI  :  10.3390/molecules19010400

来源: mdpi

【 摘 要 】

In this work, a sensitive analytical method to study the stability of two new series of synthesized heterocyclic compounds, the benzimidazole-4,7-diones 5 and N-oxide benzimidazole-4,7-dione derivatives 6 was established and validated. These derivatives were developed as potential anticancer substances to be activated under hypoxic conditions. At this point we were concerned with establishing their stability in some specific environments for further biological studies. For that, we developed and validated an RP-UPLC method. Next, selected compounds were tested in vitro for possible anticancer activity. Their effect on A549 tumour cell lines under normoxia and hypoxia conditions was determined by a WST-1 test. Four of the examined compounds (compounds 5a–c and 6c) showed very good antiproliferative effects and three of them (compounds 6a, 6b and 6d) were specific for hypoxia conditions. The hypoxia/normoxia cytotoxic coefficient of compound 6b is close to that of tirapazamine—a reference compound in our experiments—and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole).

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.