Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome

Santi M. Mandal, Anirban Chakraborty, Maidul Hossain, Denial Mahata, William F. Porto, Ranadhir Chakraborty, Chinmay K. Mukhopadhyay, Octavio L. Franco, Tapas Hazra, Amit Basak

Research output: Contribution to journalArticle

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Abstract

Amphotericin B and anidulafungin are widely used antifungal drugs for the treatment of systemic and serious mycoses. Amphotericin B is a relatively toxic drug which has long been established. This study is first of its kind to systematically investigate the nature of binding to DNA, and to evaluate intercalation of AMP-B or ANIDULA with the aid of UV-Vis, ITC, and CD spectroscopy. The binding affinity of AMP-B with exclusion sites of 4.68 base pairs (1.2 × 10<sup>5</sup> M<sup>-1</sup>) was found to be higher than that of ANIDULA with exclusion sites of 6.67 base pairs (3.78 × 10<sup>4</sup> M<sup>-1</sup>); consistent with the binding affinity values obtained for AMP-B (10<sup>5</sup> M<sup>-1</sup>) and ANIDULA (10<sup>4</sup> M<sup>-1</sup>). The binding of two drugs with double-stranded DNA was favoured by negative enthalpy as well as negative entropy changes. The intercalation of drugs to duplex polynucleotide induced changes in the intrinsic CD spectra and revealed comparatively higher affinity towards AMP-B than ANIDULA. Molecular docking studies revealed that the negative binding energy was higher in the case of AMP-B reflecting more affinity towards single-stranded DNA. The results of the cytotoxicity, immunoblotting, and gene specific LA-QPCR assay have indicated that ANIDULA is less genotoxic than AMP-B. Hence, the superiority of ANIDULA over AMP-B as a systemic antifungal drug has been established beyond doubt.

Original languageEnglish (US)
Pages (from-to)2551-2559
Number of pages9
JournalMolecular BioSystems
Volume11
Issue number9
DOIs
StatePublished - Jul 13 2015

Fingerprint

anidulafungin
Amphotericin B
Adenosine Monophosphate
Genome
DNA
Pharmaceutical Preparations
Base Pairing
Polynucleotides
Mycoses
Poisons
Single-Stranded DNA
Entropy
Immunoblotting
Spectrum Analysis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Mandal, S. M., Chakraborty, A., Hossain, M., Mahata, D., Porto, W. F., Chakraborty, R., ... Basak, A. (2015). Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome. Molecular BioSystems, 11(9), 2551-2559. https://doi.org/10.1039/c5mb00366k

Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome. / Mandal, Santi M.; Chakraborty, Anirban; Hossain, Maidul; Mahata, Denial; Porto, William F.; Chakraborty, Ranadhir; Mukhopadhyay, Chinmay K.; Franco, Octavio L.; Hazra, Tapas; Basak, Amit.

In: Molecular BioSystems, Vol. 11, No. 9, 13.07.2015, p. 2551-2559.

Research output: Contribution to journalArticle

Mandal, SM, Chakraborty, A, Hossain, M, Mahata, D, Porto, WF, Chakraborty, R, Mukhopadhyay, CK, Franco, OL, Hazra, T & Basak, A 2015, 'Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome', Molecular BioSystems, vol. 11, no. 9, pp. 2551-2559. https://doi.org/10.1039/c5mb00366k
Mandal SM, Chakraborty A, Hossain M, Mahata D, Porto WF, Chakraborty R et al. Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome. Molecular BioSystems. 2015 Jul 13;11(9):2551-2559. https://doi.org/10.1039/c5mb00366k
Mandal, Santi M. ; Chakraborty, Anirban ; Hossain, Maidul ; Mahata, Denial ; Porto, William F. ; Chakraborty, Ranadhir ; Mukhopadhyay, Chinmay K. ; Franco, Octavio L. ; Hazra, Tapas ; Basak, Amit. / Amphotericin B and anidulafungin directly interact with DNA and induce oxidative damage in the mammalian genome. In: Molecular BioSystems. 2015 ; Vol. 11, No. 9. pp. 2551-2559.
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