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. 2014 Mar;7(1):27-32.
doi: 10.2478/intox-2014-0005. Epub 2014 Jul 16.

Antioxidant action of SMe1EC2, the low-basicity derivative of the pyridoindole stobadine, in cell free chemical models and at cellular level

Aneta Balcerczyk  1 , Grzegorz Bartosz  2 , Joanna Drzewinska  1 , Łukasz Piotrowski  1 , Łukasz Pulaski  3 , Milan Stefek  4
Affiliations

Antioxidant action of SMe1EC2, the low-basicity derivative of the pyridoindole stobadine, in cell free chemical models and at cellular level

Aneta Balcerczyk et al. Interdiscip Toxicol. 2014 Mar.

Abstract

The aim of the study was to evaluate the antioxidant action of SMe1EC2, the structural analogue of the hexahydropyridoindole antioxidant stobadine. The antiradical activity of SMe1EC2 was found to be higher when compared to stobadine, as determined both in cell-free model systems of AAPH-induced oxidation of dihydrorhodamine 123 and 2',7'-dichloro-dihydrofluorescein diacetate, and in the cellular system of stimulated macrophages RAW264.7. Analysis of proliferation of HUVEC and HUVEC-ST cells revealed absence of cytotoxic effect of SMe1EC2 at concentrations below 100 µM. The antioxidant activity of SMe1EC2, superior to the parent drug stobadine, is accounted for by both the higher intrinsic free radical scavenging action and by the better bioavailability of the low-basicity SMe1EC2 relative to the high-basicity stobadine.

Keywords: SMe1EC2; antioxidant; hexahydropyridoindole; oxidative stress; stobadine.

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Figures

Figure 1
Figure 1
Chemical structure of stobadine, [(–)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3b]indole, (1)] and SMe1EC2 [(±)-cis-8-methoxy-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid ethyl ester, (2)].
Figure 2
Figure 2
SMe1EC2 (-●-) and stobadine (-○-) protect H2R123 (a) and H2DCF DA (b) from AAPH induced oxidation in a cell-free system. Results are presented as means ± SD from at least three measurements.
Figure 3
Figure 3
Effect of SMe1EC2 (-●-) and stobadine (-○-) on oxidation of H2R123 (a) or H2DCF DA (b) by RAW 264.7 macrophages. RAW 264.7 macrophages were stimulated with 100 µg/ml of LPS for 16 h and with 100 nM PMA for 30 min in a complete medium.
Figure 4
Figure 4
Effect of SMe1EC2 (-●-) and stobadine (-○-) on proliferation of HUVEC (a) and HUVEC-ST (b). MTT assay after 72-h incubation of cells with the compounds.
Figure 5
Figure 5
Effect of SMe1EC2 (-●-) and stobadine (-○-) on the migration of HUVEC after 12 (a) or 24 (b) hours.
See this image and copyright information in PMC

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