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New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells.

Rehman S, Ikram M, Khan A, Min S, Azad E, Hofer TS, Mok Kh, Baker RJ, Blake AJ, Rehman SU - Chem Cent J (2013)

Bottom Line: This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic).Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 μM whereas the sodium analog cytotoxicity did not drop down below 60%.The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan ; Department of Chemistry, Sarhad University of Science and Information Technology, Peshawar, Pakistan.

ABSTRACT

Background: Enormous interest had been paid to the coordination chemistry of alkali and alkaline metal ions because of their role inside body viz; their Li(+)/Na(+) exchange inside the cell lead to different diseases like neuropathy, hypertension, microalbuminuria, cardiac and vascular hypertrophy, obesity, and insulin resistance. It has been presumed that alkali metal ions (whether Na(+) or K(+)) coordinated to chelating ligands can cross the hydrophobic cell membrane easily and can function effectively for depolarizing the ion difference. This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic).

Results: Distinct sodium adduct (1) with dicoumarol ligand, 4-Hydroxy-3-[(4-hydroxy-2-oxo-4a,8a-dihydro-2H-chromen-3-yl)-phenyl-methyl]-chromen-2-one (L) is isolated from the saturated solution of sodium methoxide. Single crystal X-ray diffraction studies of the adduct reveals that sodium is in the form of cation attached to a methoxide, methanol and a dicoumarol ligand where carbonyl functional groups of the coumarin derivative are acting as bridges. The sodium compound (1) is also characterized by IR, (1)H-NMR, and (13)C{(1)H}-NMR spectroscopic techniques. The composition is confirmed by elemental analysis. DFT study for 1 has been carried out using B3LYP/6-13G calculations which shown the theoretical confirmation of the various bond lengths and bond angles. Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 μM whereas the sodium analog cytotoxicity did not drop down below 60%.

Conclusion: A sodium analogue (1) with medicinally important dicoumarol ligand (L) has been reported. The crystal structure and DFT study confirm the formation of cationic sodium compound with dicoumarol. The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state. Coumarin compound with sodium was observed to be less cytotoxic than the ligand, its LD50 value never dropped below 60%.

No MeSH data available.


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Atom numbering for NMR assignment of L.
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C2: Atom numbering for NMR assignment of L.

Mentions: All the manupulations were performed under argon environment using Schlenk line system. 4-hydroxycoumarin (fluka), and benzaldehyde (Sigma Aldrich) were used as received. Analytical grade methanol (Aldrich) was dehydrated and degassed prior to use. Sodium metal (Fluka) was added to methanol to produce sodium methoxide under argon. Elemental analyses were carried out on Varian Elementar II. FT-IR spectra were recorded using Shimadzo FTIR Spectrophotometer Prestige-21. 1H-NMR was measured with Bruker DPX 400 MHz (400.23 MHz) whereas, 13C{1H}NMR was recorded on Bruker AV 400 MHz (150.9 MHz) spectrometers in DMSO-d6 at room temperature. Chemical shifts were reported in ppm and standardized by observing signals for residual protons. Chemical resonances for L were assigned using structure shown in Scheme 2 and for 1 the resonances were assigned using Figure 1B. Mass spectra were recorded on a LCT Orthogonal Acceleration TOF Electrospray mass spectrometer. Single crystal analyses were carried out using oxford diffractometer. Suitable single crystals for X-ray structural analyses of 1 was mounted on a glass fibre, and the respective data were collected on the diffractometer (graphite-monochromated Mo Kα radiation, λ = 0.71073 Å) at 108(2) K. The structures were solved with the olex2.solve [47] structure solution program using Charge Flipping and refined with the olex2.refine [48] refinement package using Gauss-Newton minimisation. Crystallographic details are given in the Additional file 1. CCDC-868924 (1) data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.


New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells.

Rehman S, Ikram M, Khan A, Min S, Azad E, Hofer TS, Mok Kh, Baker RJ, Blake AJ, Rehman SU - Chem Cent J (2013)

Atom numbering for NMR assignment of L.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716688&req=5

C2: Atom numbering for NMR assignment of L.
Mentions: All the manupulations were performed under argon environment using Schlenk line system. 4-hydroxycoumarin (fluka), and benzaldehyde (Sigma Aldrich) were used as received. Analytical grade methanol (Aldrich) was dehydrated and degassed prior to use. Sodium metal (Fluka) was added to methanol to produce sodium methoxide under argon. Elemental analyses were carried out on Varian Elementar II. FT-IR spectra were recorded using Shimadzo FTIR Spectrophotometer Prestige-21. 1H-NMR was measured with Bruker DPX 400 MHz (400.23 MHz) whereas, 13C{1H}NMR was recorded on Bruker AV 400 MHz (150.9 MHz) spectrometers in DMSO-d6 at room temperature. Chemical shifts were reported in ppm and standardized by observing signals for residual protons. Chemical resonances for L were assigned using structure shown in Scheme 2 and for 1 the resonances were assigned using Figure 1B. Mass spectra were recorded on a LCT Orthogonal Acceleration TOF Electrospray mass spectrometer. Single crystal analyses were carried out using oxford diffractometer. Suitable single crystals for X-ray structural analyses of 1 was mounted on a glass fibre, and the respective data were collected on the diffractometer (graphite-monochromated Mo Kα radiation, λ = 0.71073 Å) at 108(2) K. The structures were solved with the olex2.solve [47] structure solution program using Charge Flipping and refined with the olex2.refine [48] refinement package using Gauss-Newton minimisation. Crystallographic details are given in the Additional file 1. CCDC-868924 (1) data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.

Bottom Line: This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic).Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 μM whereas the sodium analog cytotoxicity did not drop down below 60%.The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Chemical Sciences, University of Peshawar, Peshawar, Pakistan ; Department of Chemistry, Sarhad University of Science and Information Technology, Peshawar, Pakistan.

ABSTRACT

Background: Enormous interest had been paid to the coordination chemistry of alkali and alkaline metal ions because of their role inside body viz; their Li(+)/Na(+) exchange inside the cell lead to different diseases like neuropathy, hypertension, microalbuminuria, cardiac and vascular hypertrophy, obesity, and insulin resistance. It has been presumed that alkali metal ions (whether Na(+) or K(+)) coordinated to chelating ligands can cross the hydrophobic cell membrane easily and can function effectively for depolarizing the ion difference. This unique function was utilized for bacterial cell death in which K(+) has been found coordinated valinomycin (antibiotic).

Results: Distinct sodium adduct (1) with dicoumarol ligand, 4-Hydroxy-3-[(4-hydroxy-2-oxo-4a,8a-dihydro-2H-chromen-3-yl)-phenyl-methyl]-chromen-2-one (L) is isolated from the saturated solution of sodium methoxide. Single crystal X-ray diffraction studies of the adduct reveals that sodium is in the form of cation attached to a methoxide, methanol and a dicoumarol ligand where carbonyl functional groups of the coumarin derivative are acting as bridges. The sodium compound (1) is also characterized by IR, (1)H-NMR, and (13)C{(1)H}-NMR spectroscopic techniques. The composition is confirmed by elemental analysis. DFT study for 1 has been carried out using B3LYP/6-13G calculations which shown the theoretical confirmation of the various bond lengths and bond angles. Both the compounds were studied subsequently for the U2OS tumoricidal activity and it was found that L has LD50 value of 200 μM whereas the sodium analog cytotoxicity did not drop down below 60%.

Conclusion: A sodium analogue (1) with medicinally important dicoumarol ligand (L) has been reported. The crystal structure and DFT study confirm the formation of cationic sodium compound with dicoumarol. The ligand was found more active than the sodium analog attributed to the instability of 1 in solution state. Coumarin compound with sodium was observed to be less cytotoxic than the ligand, its LD50 value never dropped below 60%.

No MeSH data available.


Related in: MedlinePlus