title: Synthesis, anticancer activity and UPLC analysis of the stability of some new benzimidazole-4,7-dione derivatives.
abstract: 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).
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Muszyńskiego 1, Łódź 90-151, Poland. katarzyna.blaszczak-swiatkiewicz@umed.lodz.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Błaszczak-Swiatkiewicz
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Muszyńskiego 1, Łódź 90-151, Poland. diogo.correia.almeida@gmail.com.
authors.forename: Diogo Correia
authors.initials: DC
authors.lastname: Almeida
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Muszyńskiego 1, Łódź 90-151, Poland. mjprocha@ff.ul.pt.
authors.forename: Maria
authors.initials: M
authors.lastname: De Jesus Perry
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Muszyńskiego 1, Łódź 90-151, Poland. elzbieta.mikiciuk-olasik@umed.lodz.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Mikiciuk-Olasik
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D004355:Drug Stability; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; C031000:benzimidazole