New benzimidazole derivatives with potential cytotoxic activity--study of their stability by RP-HPLC.
Obtained benzimidazole derivatives, our next synthesized heterocyclic compounds, belong to a new group of chemical bondings with potential anticancer properties (Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2006, J Liguid Chrom Rel Tech 29: 2367-2385; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2008, Wiad Chem 62: 11-12, in Polish; Błaszczak-Świątkiewicz & Mikiciuk-Olasik, 2011, J Liguid Chrom Rel Tech 34: 1901-1912). We used HPLC analysis to determine stability of these compounds in 0.2% DMSO (dimethyl sulfoxide). Optimisation of the chromatographic system and validation of the established analytical method were performed. Reversed phases (RP-18) and a 1:1 mixture of acetate buffer (pH 4.5) and acetonitrile as a mobile phase were used for all the analysed compounds at a flow rate 1.0 mL/min. The eluted compounds were monitored using a UV detector, the wavelength was specific for compounds 6 and 9 and compounds 7 and 10. The retention time was specific for all four compounds. The used method was found to have linearity in the concentration range of (0.1 mg/mL-0.1 μg/mL) with a correlation coefficient not less than r(2)=0.9995. Statistical validation of the method proved it to be a simple, highly precise and accurate way to determine the stability of benzimidazole derivatives in 0.2% DMSO. The recoveries of all four compounds examined were in the range 99.24-100.00%. The developed HPLC analysis revealed that the compounds studied remain homogeneous in 0.2% DMSO for up to 96 h and that the analysed N-oxide benzimidazole derivatives do not disintegrate into their analogues - benzimidazole derivatives. Compounds 8, 6 and 9 exhibit the best cytotoxic properties under normoxic conditions when tested against cells of human malignant melanoma WM 115.
Department of Pharmaceutical Chemistry and Drug Analysis, Medical University, Lodz, Poland. katarzyna.blaszczak-swiatkiewicz@umed.lodz.pl
Katarzyna
K
Błaszczak-Świątkiewicz
Marek
M
Mirowski
Katarzyna
K
Kaplińska
Rafał
R
Kruszyński
Agata
A
Trzęsowska-Kruszyńska
Elżbieta
E
Mikiciuk-Olasik
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003460:Crystallization; D018360:Crystallography, X-Ray; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004355:Drug Stability; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D057230:Limit of Detection; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D012997:Solvents; D004121:Dimethyl Sulfoxide