LOCALIZATION AND ORIENTATION OF METHOXY FLAVONOIDS IN DPPC BILAYERS: EFFECT ON THEIR ANTI-PROLIFERATIVE ACTIVITY


Ragini Sinha, Urmila J. Joshi, Akshada Joshi, Girjesh Govil

Abstract


Objective: Flavones and flavonols are an important class of naturally occurring flavonoids. They are well known for their pharmacological activity. This activity is associated with the ability of flavones and flavonols to influence membrane–dependent processes. In this paper, we have reported localization, orientation and interaction, of four synthesized flavone/flavonols with 1, 2–dipalmitoyl–sn–glycero–3–phosphocholine (DPPC) bilayers. These are compared with standard flavone; chrysin (CHY) and flavonol Quercetin (QUE).

Methods: The molecules studied are 4ʹ–methoxy flavone (MF), 3ʹ,4ʹ–dimethoxyflavone (DMF), 4ʹ–methoxyflavonol (MF–ol) and 3ʹ,4ʹ–dimethoxyflavonol (DMF–ol). The techniques used are Differential Scanning Calorimetry (DSC) and multi–nuclear NMR.

Results: Highest binding to lipid bilayers is shown by DMF, followed by QUE. Based on DSC studies it is seen, that maximum interaction of MF and DMF, takes place with the hydrophobic core of lipid bilayers. DMF–ol shows formation of a heterogeneous system at higher concentrations. The 1H NMR spectra of unilamellar vesicles of DPPC, incorporated with MF, DMF and MF–ol shows significant interaction of these compounds with the alkyl chain of the hydrophobic core. MF, DMF and MF–ol acquire parallel orientation in bilayers with the B–ring pointing towards hydrophobic core, while DMF–ol acquire mixed orientation. This may be ascribed to the presence of two methoxy and one hydroxyl group on the B–ring of DMF–ol which hinders its partitioning inside the hydrophobic core of lipid bilayer. Multi–lamellar vesicles (MLV) of DPPC incorporated with flavones, show maximum increase in Chemical Shift Anisotropy in 31P spectrum of DMF. This is followed by MF. DSC.

Conclusion: NMR and binding studies indicate that DMF is partitioned deeply inside the hydrophobic core, while MF, MF–ol and DMF–ol are mostly located in the vicinity of sn–glycero region. Therefore, we conclude that DMF which penetrates deepest inside the hydrophobic core also shows the highest anti–proliferative activity against K562 and MCF–7 cancer cell lines. Its activity is also better than CHY.


Keywords


Flavones, Flavonols, DPPC, DSC, NMR, Chemical shifts, CSA

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About this article

Title

LOCALIZATION AND ORIENTATION OF METHOXY FLAVONOIDS IN DPPC BILAYERS: EFFECT ON THEIR ANTI-PROLIFERATIVE ACTIVITY

Keywords

Flavones, Flavonols, DPPC, DSC, NMR, Chemical shifts, CSA

DOI

10.22159/ijcpr.2018v10i2.25872

Date

15-03-2018

Additional Links

Manuscript Submission

Journal

International Journal of Current Pharmaceutical Research
Vol 10, Issue 2 (Mar-Apr), 2018 Page: 60-67

Online ISSN

0975-7066

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Authors & Affiliations

Ragini Sinha
National Facility for High Field NMR, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.

Urmila J. Joshi
Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India

Akshada Joshi
Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India

Girjesh Govil
Principal K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India


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