Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives
A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2016/8517243 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556142491860992 |
|---|---|
| author | Assem Barakat Hazem A. Ghabbour Abdullah Mohammed Al-Majid Qurat-ul-ain Rehan Imad Kulsoom Javaid Nimra Naveed Shaikh Sammer Yousuf M. Iqbal Choudhary Abdul Wadood |
| author_facet | Assem Barakat Hazem A. Ghabbour Abdullah Mohammed Al-Majid Qurat-ul-ain Rehan Imad Kulsoom Javaid Nimra Naveed Shaikh Sammer Yousuf M. Iqbal Choudhary Abdul Wadood |
| author_sort | Assem Barakat |
| collection | DOAJ |
| description | A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM) and 4g (IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines. |
| format | Article |
| id | doaj-art-7e0139e6e8414c349487d4b6742701e5 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-7e0139e6e8414c349487d4b6742701e52025-02-03T05:46:16ZengWileyJournal of Chemistry2090-90632090-90712016-01-01201610.1155/2016/85172438517243Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate DerivativesAssem Barakat0Hazem A. Ghabbour1Abdullah Mohammed Al-Majid2Qurat-ul-ain3Rehan Imad4Kulsoom Javaid5Nimra Naveed Shaikh6Sammer Yousuf7M. Iqbal Choudhary8Abdul Wadood9Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, PakistanDepartment of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Biochemistry, Abdul Wali Khan University, Mardan 23200, PakistanA series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM) and 4g (IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines.http://dx.doi.org/10.1155/2016/8517243 |
| spellingShingle | Assem Barakat Hazem A. Ghabbour Abdullah Mohammed Al-Majid Qurat-ul-ain Rehan Imad Kulsoom Javaid Nimra Naveed Shaikh Sammer Yousuf M. Iqbal Choudhary Abdul Wadood Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives Journal of Chemistry |
| title | Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives |
| title_full | Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives |
| title_fullStr | Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives |
| title_full_unstemmed | Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives |
| title_short | Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives |
| title_sort | synthesis x ray crystal structures biological evaluation and molecular docking studies of a series of barbiturate derivatives |
| url | http://dx.doi.org/10.1155/2016/8517243 |
| work_keys_str_mv | AT assembarakat synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT hazemaghabbour synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT abdullahmohammedalmajid synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT quratulain synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT rehanimad synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT kulsoomjavaid synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT nimranaveedshaikh synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT sammeryousuf synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT miqbalchoudhary synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives AT abdulwadood synthesisxraycrystalstructuresbiologicalevaluationandmoleculardockingstudiesofaseriesofbarbituratederivatives |