Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation
In this work, the first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) has been designed, synthesised, and evaluated for its in vitro chemical and enzymatic hydrolysis stability. Predicted in silico physicochemical properties of the newly synthesised hybrid (3) dem...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1928111 |
| _version_ | 1829463861123612672 |
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| author | Loredana Salerno Luca Vanella Valeria Sorrenti Valeria Consoli Valeria Ciaffaglione Antonino N. Fallica Vittorio Canale Paweł Zajdel Rosario Pignatello Sebastiano Intagliata |
| author_facet | Loredana Salerno Luca Vanella Valeria Sorrenti Valeria Consoli Valeria Ciaffaglione Antonino N. Fallica Vittorio Canale Paweł Zajdel Rosario Pignatello Sebastiano Intagliata |
| author_sort | Loredana Salerno |
| collection | DOAJ |
| description | In this work, the first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) has been designed, synthesised, and evaluated for its in vitro chemical and enzymatic hydrolysis stability. Predicted in silico physicochemical properties of the newly synthesised hybrid (3) demonstrated a drug-like profile with suitable Absorption, Distribution, Metabolism, and Excretion (ADME) properties and low toxic liabilities. Preliminary cytotoxicity evaluation towards human prostate (DU145) and lung (A549) cancer cell lines demonstrated that 3 exerted a similar effect on cell viability to that produced by the reference drug 5-FU. Among the two tested cancer cell lines, the A549 cells were more susceptible for 3. Of note, hybrid 3 also had a significantly lower cytotoxic effect on healthy human lung epithelial cells (BEAS-2B) than 5-FU. Altogether our results served as an initial proof-of-concept to develop 5-FU/HO-1 mutual prodrugs as potential novel anticancer agents. |
| first_indexed | 2024-12-13T13:38:05Z |
| format | Article |
| id | doaj.art-d08b3debd1ad442da383fcfbf840908f |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:38:05Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-d08b3debd1ad442da383fcfbf840908f2022-12-21T23:43:41ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-013611377138510.1080/14756366.2021.19281111928111Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluationLoredana Salerno0Luca Vanella1Valeria Sorrenti2Valeria Consoli3Valeria Ciaffaglione4Antonino N. Fallica5Vittorio Canale6Paweł Zajdel7Rosario Pignatello8Sebastiano Intagliata9Department of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaDepartment of Organic Chemistry, Jagiellonian University Medical CollegeDepartment of Organic Chemistry, Jagiellonian University Medical CollegeDepartment of Drug and Health Sciences, University of CataniaDepartment of Drug and Health Sciences, University of CataniaIn this work, the first mutual prodrug of 5-fluorouracil and heme oxygenase1 inhibitor (5-FU/HO-1 hybrid) has been designed, synthesised, and evaluated for its in vitro chemical and enzymatic hydrolysis stability. Predicted in silico physicochemical properties of the newly synthesised hybrid (3) demonstrated a drug-like profile with suitable Absorption, Distribution, Metabolism, and Excretion (ADME) properties and low toxic liabilities. Preliminary cytotoxicity evaluation towards human prostate (DU145) and lung (A549) cancer cell lines demonstrated that 3 exerted a similar effect on cell viability to that produced by the reference drug 5-FU. Among the two tested cancer cell lines, the A549 cells were more susceptible for 3. Of note, hybrid 3 also had a significantly lower cytotoxic effect on healthy human lung epithelial cells (BEAS-2B) than 5-FU. Altogether our results served as an initial proof-of-concept to develop 5-FU/HO-1 mutual prodrugs as potential novel anticancer agents.http://dx.doi.org/10.1080/14756366.2021.1928111mutual prodrugshybrid compoundsanticancer agents5-fluorouracilheme oxygenase 1ho-1 inhibitors |
| spellingShingle | Loredana Salerno Luca Vanella Valeria Sorrenti Valeria Consoli Valeria Ciaffaglione Antonino N. Fallica Vittorio Canale Paweł Zajdel Rosario Pignatello Sebastiano Intagliata Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation Journal of Enzyme Inhibition and Medicinal Chemistry mutual prodrugs hybrid compounds anticancer agents 5-fluorouracil heme oxygenase 1 ho-1 inhibitors |
| title | Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation |
| title_full | Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation |
| title_fullStr | Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation |
| title_full_unstemmed | Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation |
| title_short | Novel mutual prodrug of 5-fluorouracil and heme oxygenase-1 inhibitor (5-FU/HO-1 hybrid): design and preliminary in vitro evaluation |
| title_sort | novel mutual prodrug of 5 fluorouracil and heme oxygenase 1 inhibitor 5 fu ho 1 hybrid design and preliminary in vitro evaluation |
| topic | mutual prodrugs hybrid compounds anticancer agents 5-fluorouracil heme oxygenase 1 ho-1 inhibitors |
| url | http://dx.doi.org/10.1080/14756366.2021.1928111 |
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