New benzimidazole derivatives with potential cytotoxic activity--study of their stability by RP-HPLC.

Abstract

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.

Antiproliferative activity of new benzimidazole derivatives.

“…Selected compounds were purified on a Waters 600 LC HPLC system with a Supelco RP-18 column (15 cm × 4 mm × 5 μm plus symmetry C18 guard, Waters) held at 20 o C. Chromatographic peaks were identified with a UV detector (Waters) (Błaszczak-Świątkiewicz et al, 2012).…”

“…The synthetic process included reactions -Scheme 1. The structure of the new benzimidazole derivatives was established by X-ray crystal structure analysis (Błaszczak-Świątkiewicz et al, 2012).…”

Benzimidazole Scaffold as Anticancer Agent: Synthetic Approaches and Structure–Activity Relationship

“…The title compounds were then screened for their in vitro anticancer activity at NCI 60 cell line panel of which compound 514l emerged as lead compound. Blaszczak‐Swiatkiewicz et al synthesised new benzimidazole derivatives (Scheme ) and characterised them for anticancer activity against the reference compound tirapazamine. Compounds 517a , 517c and 518a exhibited potent properties when tested against cells of human malignant melanoma WM115 with Trypan blue test.…”

Cytotoxic and Antimicrobial Properties of Copper(II) Complexes of Pyridine and Benzimidazole Derivatives

“…Thus copper‐based complexes are regarded as potential anticancer agents among non‐platinum compounds. What more, benzimidazole and many of its derivatives exhibit a variety of biological actions such as antiviral, antibacterial, anticancer, and anifungal activity . Their connections with copper ions could probably possess the enhanced activity.…”