Chemotherapeutic potential of 9-phenyl acridine: biophysical studies on its binding to DNA |
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Authors: | Rita Ghosh Sudipta Bhowmik Angshuman Bagchi Dipankar Das Somnath Ghosh |
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Institution: | (1) Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, WB, India;(2) Present address: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA;(3) Organic Section, Department of Chemistry, Jadavpur University, Jadavpur, 700032, WB, India |
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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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