DNA binding, anti-tumour activity and reactivity toward cell thiols of acridin-9-ylalkenoic derivatives
In this paper, we describe the synthesis, biochemical properties and biological activity of a series of new 9-substituted acridine derivatives with a reactive alkene moiety: 9-[(E)-2-phenylethenyl] acridine ( 1 ) and methyl (2E)-3-(acridin-9-yl)-prop-2-enoate ( 2 ). The interaction of derivatives 1...
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| Published in: | Journal of chemical sciences (Bangalore, India) Vol. 127; no. 5; pp. 931 - 940 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
New Delhi
Springer India
01-05-2015
|
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | In this paper, we describe the synthesis, biochemical properties and biological activity of a series of new 9-substituted acridine derivatives with a reactive alkene moiety: 9-[(E)-2-phenylethenyl] acridine (
1
) and methyl (2E)-3-(acridin-9-yl)-prop-2-enoate (
2
). The interaction of derivatives
1
and
2
with calf thymus DNA was investigated using UV-Vis, fluorescence and circular dichroism spectroscopy. The binding constants K were estimated as being in the range of 1.9 to 7.1 × 10
5
M
−1
, and the percentage of hypochromism was found to be 40–57% (from spectral titration). UV-Vis, fluorescence, and CD measurements indicate that the compounds were effective DNA-intercalating agents. Electrophoretic separation proved that ligands
1
and
2
relaxed topoisomerase I at a concentration of 5
μ
M. Ester
2
was shown to have a stronger cytostatic effect on leukemia cell line L1210 than alkene
1
. The incubation of ligands
1
and
2
with the ovarian carcinoma cell line A2780 confirmed their extensive cytotoxic effects, an effect which was particularly pronounced in the case of ligand
2
. Cytotoxicity tests against A2780 cells demonstrate that a conjugate of compound
2
with
L
-cysteine (
3
) is less cytotoxic than compound
2
, especially at concentrations greater than 10
μ
M.
Graphical Abstract
Synthesis and biological activity of a series of novel acridine derivatives (1-3) are described. The interaction of these compounds with DNA indicates that the compounds are effective DNA-intercalating agents. Electrophoretic separation proved that the ligands relaxed topoisomerase I. The incubation of the derivatives with A2780 and L1210 cell lines confirmed their cytotoxic effects. |
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| ISSN: | 0974-3626 0973-7103 |
| DOI: | 10.1007/s12039-015-0851-9 |