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. 2022 Oct 28;12(48):30936-30951.
doi: 10.1039/d2ra05072b. eCollection 2022 Oct 27.

Exploring inclusion complex of an anti-cancer drug (6-MP) with β-cyclodextrin and its binding with CT-DNA for innovative applications in anti-bacterial activity and photostability optimized by computational study

Modhusudan Mondal  1 , Shatarupa Basak  1 , Salim Ali  1 , Debadrita Roy  1 , Subhadeep Saha  2 , Biswajit Ghosh  1 , Narendra Nath Ghosh  3 , Khusboo Lepcha  4 , Kanak Roy  5 , Mahendra Nath Roy  1   6
Affiliations

Exploring inclusion complex of an anti-cancer drug (6-MP) with β-cyclodextrin and its binding with CT-DNA for innovative applications in anti-bacterial activity and photostability optimized by computational study

Modhusudan Mondal et al. RSC Adv. .

Abstract

The co-evaporation approach was used to examine the host-guest interaction and to explore the cytotoxic and antibacterial properties of an important anti-cancer medication, 6-mercaptopurine monohydrate (6-MP) with β-cyclodextrin (β-CD). The UV-Vis investigation confirmed the inclusion complex's (IC) 1 : 1 stoichiometry and was also utilized to oversee the viability of this inclusion process. FTIR, NMR, and XRD, among other spectrometric techniques, revealed the mechanism of molecular interactions between β-CD and 6-MP which was further hypothesized by DFT to verify tentative outcomes. TGA and DSC studies revealed that 6-MP's thermal stability increased after encapsulation. Because of the protection of drug 6-MP by β-CD, the formed IC was found to have higher photostability. This work also predicts the release behavior of 6-MP in the presence of CT-DNA without any chemical changes. An evaluation of the complex's antibacterial activity in vitro revealed that it was more effective than pure 6-MP. The in vitro cytotoxic activity against the human kidney cancer cell line (ACHN) was also found to be significant for the IC (IC50 = 4.18 μM) compared to that of pure 6-MP (IC50 = 5.49 μM). These findings suggest that 6-MP incorporation via β-CD may result in 6-MP stability and effective presentation of its solubility, cytotoxic and antibacterial properties.

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Conflict of interest statement

There were no known financial or personal conflicts of interest amongst the authors that could have influenced the work provided in this publication.

Figures

Fig. 1
Fig. 1. Generation of Job plot (a) spectra and (b) the obtained Job plot.
Fig. 2
Fig. 2. Variations in the surface tension of the 6-MP with increasing concentration of (a) β-CD.
Fig. 3
Fig. 3. Absorption spectra of 6-MP (40 μM) in various concentrations of aqueous (a) β-CD in μM.
Fig. 4
Fig. 4. 1H NMR spectra of (a) β-CD, (b) 6-MP, and (c) IC.
Fig. 5
Fig. 5. FTIR spectra of 6-MP, β-CD, and 6-MP-β-CD IC.
Fig. 6
Fig. 6. Top and side views of the optimized geometries for the 6-MP-β-CD complex at M06-2X/6-31+G(d) level of theory. Red, gray, white, blue and yellow color represents oxygen, carbon, hydrogen, nitrogen and sulfur atoms respectively.
Fig. 7
Fig. 7. SEM images of (a) β-CD, (b) 6-MP, and their (c) IC.
Fig. 8
Fig. 8. PXRD spectra of β-CD, 6-MP and its IC.
Fig. 9
Fig. 9. DSC thermograms of β-CD, 6-MP and its IC.
Fig. 10
Fig. 10. (a) TGA of β-CD, 6-MP and its IC.
Fig. 11
Fig. 11. UV-spectra of 6-MP+β-CD of different concentrations (mg mL−1) in aqueous medium (a) 0.033, (b) 0.066, (c) 0.099, (d) 0.132, (e) 0.165, (f) 0.198, and (g) 0.228.
Fig. 12
Fig. 12. Time-dependent UV-Vis spectra of (a) 6-MP, (b) IC and (c) percentage of degradation of each component under sunlight.
Fig. 13
Fig. 13. UV-Vis spectra of (a) 6-MP (b) IC at different concentrations of CT-DNA.
Fig. 14
Fig. 14. IC and 6-MP cytotoxicity percentages at various concentrations.
Fig. 15
Fig. 15. HOMO and LUMO charge densities of the 6-MP-β-CD complex.
Fig. 16
Fig. 16. Electrostatic potential maps for the 6-MP-β-CD complex.
Fig. 17
Fig. 17. Plots of reduced density gradient (RDG) for 6-MP-β-CD complex.
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