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Chemotherapeutic potential of 9-phenyl acridine: biophysical studies on its binding to DNA

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Abstract

Acridines and their derivatives are well-known probes for nucleic acids as well as being relevant in the field of drug development to establish new chemotherapeutic agents. We have shown from molecular modelling studies that 9-phenyl acridine and some of its derivatives can act as inhibitors of topoisomerase I and thus have potential to act as anticancer agents. Rational design of new compounds for therapeutics requires knowledge about their structural stability and interactions with various cellular macromolecules. In this regard it is important to know how these molecules would interact with DNA. Here we report the interaction of 9-phenyl acridine (ACPH) with calf thymus DNA (CT-DNA) based on various biophysical and molecular modelling studies. Spectrophotometric studies indicated that ACPH binds to CT-DNA. DNA melting studies revealed that binding of ACPH to CT-DNA resulted in a small increase in melting temperature, which is unlikely in case of classical intercalator; rather, it indicates external binding. Viscosity measurements show that ACPH exhibits groove binding. Competitive binding of ACPH to CT-DNA pre-bound to ethidium bromide (EB) showed slow quenching. Measurement of the binding constant of ACPH by fluorescent intercalator displacement (FID) assay corroborated the notion that there was groove binding. Molecular modelling studies also supported this finding. Results indicate that binding of ACPH is through partial intercalation in the minor groove of DNA.

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Abbreviations

ACPH:

9-Phenyl acridine

T m :

DNA melting temperature

FID:

Fluorescent intercalator displacement

EB:

Ethidium bromide

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Acknowledgments

The authors are grateful to the University of Kalyani for providing a fellowship to Sudipta Bhowmik.

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Author notes

  1. Angshuman Bagchi

    Present address: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA, 94945, USA

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, WB, India

    Rita Ghosh, Sudipta Bhowmik & Angshuman Bagchi

  2. Organic Section, Department of Chemistry, Jadavpur University, Jadavpur, 700032, WB, India

    Dipankar Das & Somnath Ghosh

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  1. Rita Ghosh
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  2. Sudipta Bhowmik
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Correspondence to Rita Ghosh.

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Ghosh, R., Bhowmik, S., Bagchi, A. et al. Chemotherapeutic potential of 9-phenyl acridine: biophysical studies on its binding to DNA. Eur Biophys J 39, 1243–1249 (2010). https://doi.org/10.1007/s00249-010-0577-z

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  • DOI: https://doi.org/10.1007/s00249-010-0577-z

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