Cargando…

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

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Rehman, Sadia, Ikram, Muhammad, Khan, Ajmal, Min, Soyoung, Azad, Effat, Hofer, Thomas S, Mok, KH, Baker, Robert J, Blake, Alexander J, Rehman, Saeed Ur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716688/
https://www.ncbi.nlm.nih.gov/pubmed/23819586
http://dx.doi.org/10.1186/1752-153X-7-110
_version_ 1782277576448802816
author Rehman, Sadia
Ikram, Muhammad
Khan, Ajmal
Min, Soyoung
Azad, Effat
Hofer, Thomas S
Mok, KH
Baker, Robert J
Blake, Alexander J
Rehman, Saeed Ur
author_facet Rehman, Sadia
Ikram, Muhammad
Khan, Ajmal
Min, Soyoung
Azad, Effat
Hofer, Thomas S
Mok, KH
Baker, Robert J
Blake, Alexander J
Rehman, Saeed Ur
author_sort Rehman, Sadia
collection PubMed
description 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 LD(50) 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 LD(50) value never dropped below 60%.
format Online
Article
Text
id pubmed-3716688
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-37166882013-07-20 New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells Rehman, Sadia Ikram, Muhammad Khan, Ajmal Min, Soyoung Azad, Effat Hofer, Thomas S Mok, KH Baker, Robert J Blake, Alexander J Rehman, Saeed Ur Chem Cent J Preliminary Communication 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 LD(50) 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 LD(50) value never dropped below 60%. BioMed Central 2013-07-02 /pmc/articles/PMC3716688/ /pubmed/23819586 http://dx.doi.org/10.1186/1752-153X-7-110 Text en Copyright © 2013 Rehman et al.; licensee Chemistry Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Preliminary Communication
Rehman, Sadia
Ikram, Muhammad
Khan, Ajmal
Min, Soyoung
Azad, Effat
Hofer, Thomas S
Mok, KH
Baker, Robert J
Blake, Alexander J
Rehman, Saeed Ur
New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title_full New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title_fullStr New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title_full_unstemmed New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title_short New dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
title_sort new dicoumarol sodium compound: crystal structure, theoretical study and tumoricidal activity against osteoblast cancer cells
topic Preliminary Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716688/
https://www.ncbi.nlm.nih.gov/pubmed/23819586
http://dx.doi.org/10.1186/1752-153X-7-110
work_keys_str_mv AT rehmansadia newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT ikrammuhammad newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT khanajmal newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT minsoyoung newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT azadeffat newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT hoferthomass newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT mokkh newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT bakerrobertj newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT blakealexanderj newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells
AT rehmansaeedur newdicoumarolsodiumcompoundcrystalstructuretheoreticalstudyandtumoricidalactivityagainstosteoblastcancercells