Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study
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2015
Authors
Veselinović, JovanaKocić, Gordana M.
Pavić, Aleksandar
Nikodinović-Runić, Jasmina
Šenerović, Lidija
Nikolić, Goran M.
Veselinović, Aleksandar
Article (Published version)
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A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in compari...son to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.
Keywords:
4-Phenyl hydroxycoumarins / Cytotoxicity / Molecular docking / Teratogenic potential / Protein kinase inhibitorsSource:
Chemico-biological Interactions, 2015, 231, 10-17Publisher:
- Elsevier Ireland Ltd, Clare
Funding / projects:
- Production of new dietetic milk products for risk populations based on qualitative and quantitative analysis of health risk markers in milk consumption (RS-MESTD-Technological Development (TD or TR)-31060)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-MESTD-Basic Research (BR or ON)-173048)
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3410
DOI: 10.1016/j.cbi.2015.02.011
ISSN: 0009-2797
PubMed: 25724286
WoS: 000353741100002
Scopus: 2-s2.0-84924024816
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Institution/Community
Inovacioni centar / Innovation CentreTY - JOUR AU - Veselinović, Jovana AU - Kocić, Gordana M. AU - Pavić, Aleksandar AU - Nikodinović-Runić, Jasmina AU - Šenerović, Lidija AU - Nikolić, Goran M. AU - Veselinović, Aleksandar PY - 2015 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1699 AB - A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile. PB - Elsevier Ireland Ltd, Clare T2 - Chemico-biological Interactions T1 - Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study VL - 231 SP - 10 EP - 17 DO - 10.1016/j.cbi.2015.02.011 ER -
@article{ author = "Veselinović, Jovana and Kocić, Gordana M. and Pavić, Aleksandar and Nikodinović-Runić, Jasmina and Šenerović, Lidija and Nikolić, Goran M. and Veselinović, Aleksandar", year = "2015", abstract = "A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.", publisher = "Elsevier Ireland Ltd, Clare", journal = "Chemico-biological Interactions", title = "Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study", volume = "231", pages = "10-17", doi = "10.1016/j.cbi.2015.02.011" }
Veselinović, J., Kocić, G. M., Pavić, A., Nikodinović-Runić, J., Šenerović, L., Nikolić, G. M.,& Veselinović, A.. (2015). Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study. in Chemico-biological Interactions Elsevier Ireland Ltd, Clare., 231, 10-17. https://doi.org/10.1016/j.cbi.2015.02.011
Veselinović J, Kocić GM, Pavić A, Nikodinović-Runić J, Šenerović L, Nikolić GM, Veselinović A. Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study. in Chemico-biological Interactions. 2015;231:10-17. doi:10.1016/j.cbi.2015.02.011 .
Veselinović, Jovana, Kocić, Gordana M., Pavić, Aleksandar, Nikodinović-Runić, Jasmina, Šenerović, Lidija, Nikolić, Goran M., Veselinović, Aleksandar, "Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study" in Chemico-biological Interactions, 231 (2015):10-17, https://doi.org/10.1016/j.cbi.2015.02.011 . .