New benzimidazole derivatives with potential cytotoxic activity - study of their stability by RP-HPLC
Treść / Zawartość
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 r2=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.
- Albertella MR, Loadman PM, Jones PH (2008) Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study. Clin Cancer Res 14: 1096-1104.
- Błaszczak-Świątkiewicz K, Mikiciuk-Olasik E (2006) HPLC method for determination of stability of new quinazoline derivaies. J Liq Chromatogr Relat Technol 29: 2367-2385.
- Błaszczak-Świątkiewicz K, Mikiciuk-Olasik E (2008) Role of hipoxia in advancesin new anticancer diagnostics and therapy. Wiad Chem 62: 1066-1089 (in Polish).
- Błaszczak-Świątkiewicz K, Mikiciuk-Olasik E (2011) Application of HPLC method for investigation of stability of new benzimidazole derivatives. J Liq Chromatogr Relat Technol 34: 1901-1912.
- Brown J M (1999) The hypoxic cell: a target for selective cancer therapy. Cancer Res 59: 5863-5870.
- Budzisz E, Miernicka M, Lorenz IP, Mayer P, Balcerzak E, Krajewska U, Rozalski M (2010) Synthesis, X-ray structures and cytotoxic activity of platinum(II), palladium(II) and copper(II) complexes with chelating ligands. Eur J Med Chem 45: 2613-2621.
- Coban G, Zencir S, Zupko I, Réthy B, Gunes HS, Topcu Z (2009) Synthesis and biological activity evaluation of 1H-benzimidazoles via mammalian DNA topoisomerase I and cytostaticity assays. Eur J Med Chem 44: 2280-2285.
- Cowan DSM, Matejovic JF, McClelland RA, Ruth AM (1994) DNA-targeted 2-nitroimidazoles: in vivo and in vitro studies. Br J Cancer 70: 1067-1074.
- Denny WA (2000) The role of hypoxia-activated prodrugs in cancer therapy. Lancet Oncol 1: 25-29.
- Desiraju GR, Steiner T (1999) The Weak Hydrogen Bond in Structural Chemistry and Biolog. Oxford University Press.
- Jerchel D, Fischer H, Kracht M (1952) Zur darstellung der benzimidazole. Justus Liebigs Ann Chem 575: 162.
- Gupta M, Fan S, Zhan Q, Kohn KW, O'Connor PM and Pommier Y (1997) Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells. Clin Cancer Res 3: 1653-1660.
- Koch CJ (1993) Unusual oxygen concentration dependence of toxicity of SR-4233, a hypoxic celltoxin. Cancer Res 53: 3992-3997.
- Lin A, Cosby LA, Shansky ChW, Sartorelli AC. (1972) Potential Bioreductive alkylating agents. Benzoquinone derivatives. J Med Chem 15: 1247-1251.
- McKeown SR, Cowen RL, Williams KJ (2007) Bioreductive Drugs: from Concept to Clinic. Clin Oncol (R Coll Radiol) 19: 427-442.
- McKeown SR, Friery OP, McIntyre IA, Hejmadi MV, Paterson LH, Hirst DG (1996) Evidence for a therapeutic gain when AQ4N or tirapazamine is combined with radiation. Br J Cancer Suppl 27: S39-S42.
- Kaczirek K, Schindl M, Weinhäusel A, Scheuba C, Passler C, Prager G, Raderer M, Hamilton G, Mittlböck M, Siegl V, Pfragner RB Niederle (2004) Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines. J Clin Endocrinol Metab 89: 2397-2401.
- Mikiciuk-Olasik E, Błaszczak-Świątkiewicz K, Żurek E, Krajewska U, Różalski M, Kruszyński R, Bartczak TJ (2004) New derivatives of quinazoline and 1,2-dihydroquinazoline N3-oxide with expected antitumour acivity. Arch Pharm Pharm Med Chem 337: 239-246.
- Panieres GC, Bonifas IA, Guadalupe JC, Lopez JE, Guadalupe G, Alvarez CT (2000) Synthesis of benzimidazoles in dry medium. Synth Commun 30: 2195.
- Preston PN (1974) Synthesis, reactions and spectroscopic properties of benzimidazoles. Chem Rev 74: 279-3145.
- Selcen A, Semih HG, Topcu Z (2007) 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors. Acta Biochim Pol 54: 561-565.
- Selcen AA, Zencir S, Zupko I, Coban G, Rethy B, Gunes SH, Topcu Z (2009) Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells. J Enzyme Inhib Med Chem 24: 844-849.
- Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr A 64: 112-122.
- Singh M, Tandon V (2011) Synthesis and biological activity of novel inhibitors of topoisomerase I: 2-Aryl-substituted 2-bis-1H-benzimidazoles. Eur J Med Chem 46: 659-669.
- Tanizawa A, Fujimori A, Fujimori Y, Pommier Y (1994) Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials. J Nat Cancer Inst 86: 836-842.
- X-RED (1999) Version 1.18. STOE & Cie GmbH, Darmstadt, Germany.
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