Abstract:
:Recent reports suggest influence of anti-cancer anthracyclines on telomere dysfunction and their possible interaction with G-quadruplex (G4) DNA as an alternate pathway to apoptosis. We have investigated interaction of epirubicin and adriamycin with G4 DNA [d-AGGG(TTAGGG)3] comprising human telomeric DNA sequence by surface plasmon resonance, absorption, fluorescence, circular dichroism and thermal denaturation. Epirubicin and adriamycin bind with affinity, Kb, = 2.5×105 and 5.2×105M-1, respectively in monomeric form leading to decrease in absorbance, fluorescence quenching and ellipticity changes without any significant shift in absorption emission maxima with corresponding induced thermal stabilization by 13.0 and 11.6°C in K+ rich solution. Na+ ions did not induce any thermal stabilization. Molecular docking confirmed external binding at grooves and loops of G4 DNA involving 4OCH3 of ring D, 9COCH2OH of ring A, 4'OH/H and 3'NH3+ of daunosamine sugar. Thermal stabilization induced by specific interactions is likely to hamper telomere association with telomerase enzyme and contribute to drug-induced apoptosis in cancer cell lines besides causing damage to duplex DNA. The findings pave the way for drug designing in view of immense possibilities of altering substituent groups on anthracyclines for enhancement of efficacy, reduced cell toxicity as well as specificity towards G-quadruplex DNA.
journal_name
Int J Biol Macromoljournal_title
International journal of biological macromoleculesauthors
Raje S,Barthwal Rdoi
10.1016/j.ijbiomac.2019.08.109subject
Has Abstractpub_date
2019-10-15 00:00:00pages
1272-1287eissn
0141-8130issn
1879-0003pii
S0141-8130(19)33876-0journal_volume
139pub_type
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journal_title:International journal of biological macromolecules
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