Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies
In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier Ltd
2015
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| Online Access: | http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf |
| _version_ | 1848818458457800704 |
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| author | Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub |
| author_facet | Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub |
| author_sort | Rauf, Abdul |
| building | UMP Institutional Repository |
| collection | Online Access |
| description | In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53±0.027, 8.93±0.027, 12.96±0.13, 15±0.098, 18.9±0.027 and 19.7±0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21±0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83±0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns. |
| first_indexed | 2025-11-15T01:37:59Z |
| format | Article |
| id | ump-9307 |
| institution | Universiti Malaysia Pahang |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T01:37:59Z |
| publishDate | 2015 |
| publisher | Elsevier Ltd |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | ump-93072018-04-19T02:39:43Z http://umpir.ump.edu.my/id/eprint/9307/ Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub Q Science (General) In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53±0.027, 8.93±0.027, 12.96±0.13, 15±0.098, 18.9±0.027 and 19.7±0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21±0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83±0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns. Elsevier Ltd 2015 Article PeerReviewed application/pdf en http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf Rauf, Abdul and Shahzad, Sohail Anjum and Bajda, Marek and Yar, Muhammad and Ahmed, Faiz and Hussain, Nazar and Akhtar, Muhammad Nadeem and Khan, Ajmal and Jończyk, Jakub (2015) Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies. Bioorganic & Medicinal Chemistry, 23 (17). pp. 6049-6058. ISSN 0968-0896. (Published) http://dx.doi.org/10.1016/j.bmc.2015.05.038 doi: 10.1016/j.bmc.2015.05.038 |
| spellingShingle | Q Science (General) Rauf, Abdul Shahzad, Sohail Anjum Bajda, Marek Yar, Muhammad Ahmed, Faiz Hussain, Nazar Akhtar, Muhammad Nadeem Khan, Ajmal Jończyk, Jakub Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title | Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title_full | Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title_fullStr | Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title_full_unstemmed | Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title_short | Design and Synthesis of New Barbituric- and Thiobarbituric Acid Derivatives as Potent Urease Inhibitors: Structure Activity Relationship and Molecular Modeling Studies |
| title_sort | design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: structure activity relationship and molecular modeling studies |
| topic | Q Science (General) |
| url | http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/ http://umpir.ump.edu.my/id/eprint/9307/1/Design%20and%20Synthesis%20of%20New%20Barbituric-%20and%20Thiobarbituric%20Acid%20Derivatives%20as%20Potent%20Urease%20Inhibitors-%20Structure%20Activity%20Relationship%20And%20Molecular%20Modeling%20Studies.pdf |