Molecular encapsulation of berberine and ethidium bromide in anthraquinonecarboxamido-β-cyclodextrin conjugate: supramolecular association with DNA duplex and G-quadruplexes

Abstract

G-quadruplex DNA in recognized as a potential target for anti-cancer drugs. In this work, an anthraquinonecarboxamido derivative of β-cyclodextrin (AQCC) is synthesized as a novel DNA binder that further can deliver an additional molecule at the target, carrying it in the cavity of modified cyclodextrin. The binding of AQCC with ethidium bromide (EtBr), berberine (Ber), duplex calf-thymus DNA (CT-DNA), quadruplexes (G4) viz., kit22, myc22, and telo24 are studied. The compound acts as a host molecule for the encapsulation of DNA binders viz., EtBr, Ber and enhances their fluorescence due to the encapsulation in its AQCC’s cyclodextrin cavity. The binding constant of the host: guest complex of EtBr and Ber with AQCC’s cavity are 6.4 × 10⁵ and 3.3 × 10⁶ mol⁻¹ dm³, respectively. The proximity of the protons of the guest and host molecules is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY). The conjugate displays a quenching of fluorescence selectively on the association with CT-DNA and quadruplex kit22 that is contrast to the spectral behavior with quadruplex myc22 and telo24. CT-DNA exhibits dissimilar fluorescence spectra in free- and EtBr-bound forms. In addition, kit22 exhibit dissimilar emission profile when AQCC encapsulates Ber. Therefore, the Ber-loaded complexes and the AQCC molecule bind to different G-quadruplexes with different binding strengths. In addition, the effect of Ber in binding to the target DNAs is pronounces since the Ber molecule has more affinity to bind to quadruplexes than the duplex.

Graphical Abstract

Keywords:

• Anthraquinone
• β-cyclodextrin
• G-quadruplex
• calf-thymus DNA
• binding constant
• host: guest complex

Acknowledgement

The authors express their gratitude to the Department of Atomic Energy-Board of Research in Nuclear Sciences, Government of India, for the project 37(2)/14/17/2018-BRNS.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors express their gratitude to the Department of Atomic Energy-Board of Research in Nuclear Sciences, Government of India, for the project 37(2)/14/17/2018-BRNS.