Synthesis, Anticancer Activity and UPLC Analysis of the Stability of Some New Benzimidazole-4,7-dione Derivatives
| Autor: | Xiya Ma, Xiu-Zhong Hu, Hao-Ze Yu, Jun Zhao, Weiyun Shi, Qian Wen, Tingjun Fan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Misonidazole
Corneal endothelium N-oxide benzimidazole-4 7-dione Pharmaceutical Science Antineoplastic Agents Biology Article Analytical Chemistry lcsh:QD241-441 chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship benzimidazole-4 7-dione Drug Stability lcsh:Organic chemistry Cell Line Tumor Drug Discovery medicine Structure–activity relationship Humans Physical and Theoretical Chemistry Cell Proliferation UPLC Molecular Structure hypoxia Organic Chemistry Mitomycin C Reproducibility of Results Hypoxia (medical) In vitro Cell Hypoxia Transplantation chemistry Biochemistry Chemistry (miscellaneous) Cell culture anticancer prodrug Molecular Medicine Benzimidazoles medicine.symptom Chromatography Liquid |
| Zdroj: | Molecules, Vol 19, Iss 1, Pp 400-413 (2013) Molecules Molecules; Volume 19; Issue 1; Pages: 400-413 |
| ISSN: | 1420-3049 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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