Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors
Thymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipin...
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Taylor & Francis Group
2020-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2020.1759581 |
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doaj-dde8a52c122b40dab2682605bcecf3482021-07-15T13:10:32ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742020-01-013511116112310.1080/14756366.2020.17595811759581Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitorsZohor Mohammad Mahdi Alzhrani0Mohammad Mahboob Alam1Thikryat Neamatallah2Syed Nazreen3Department of Chemistry, Faculty of Science, Albaha UniversityDepartment of Chemistry, Faculty of Science, Albaha UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz UniversityDepartment of Chemistry, Faculty of Science, Albaha UniversityThymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipinski and Veber rules which indicated good drug likeness properties upon oral administration. Among the synthesised hybrids, compound 9 and 10 displayed 4.5 and 4.4 folds activity of 5-Fluorouracil, respectively against MCF-7 cell line whereas 3.1 and 2.5 folds cytotoxicity against HCT-116 cell line. Furthermore, compound 9 and 10 also inhibited TS enzyme with IC50 = 1.67 and 2.21 µM, respectively. Finally, the docking studies of 9 and 10 were found to be consistent with in vitro TS results. From these studies, compound 9 and 10 has the potential to be developed as TS inhibitors.http://dx.doi.org/10.1080/14756366.2020.17595812,4-thiazolidinediones1,3,4-oxadiazolesthymidylate synthasemolecular dockingpharmacokinetics |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Zohor Mohammad Mahdi Alzhrani Mohammad Mahboob Alam Thikryat Neamatallah Syed Nazreen |
| spellingShingle |
Zohor Mohammad Mahdi Alzhrani Mohammad Mahboob Alam Thikryat Neamatallah Syed Nazreen Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry 2,4-thiazolidinediones 1,3,4-oxadiazoles thymidylate synthase molecular docking pharmacokinetics |
| author_facet |
Zohor Mohammad Mahdi Alzhrani Mohammad Mahboob Alam Thikryat Neamatallah Syed Nazreen |
| author_sort |
Zohor Mohammad Mahdi Alzhrani |
| title |
Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| title_short |
Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| title_full |
Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| title_fullStr |
Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| title_full_unstemmed |
Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| title_sort |
design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors |
| publisher |
Taylor & Francis Group |
| series |
Journal of Enzyme Inhibition and Medicinal Chemistry |
| issn |
1475-6366 1475-6374 |
| publishDate |
2020-01-01 |
| description |
Thymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipinski and Veber rules which indicated good drug likeness properties upon oral administration. Among the synthesised hybrids, compound 9 and 10 displayed 4.5 and 4.4 folds activity of 5-Fluorouracil, respectively against MCF-7 cell line whereas 3.1 and 2.5 folds cytotoxicity against HCT-116 cell line. Furthermore, compound 9 and 10 also inhibited TS enzyme with IC50 = 1.67 and 2.21 µM, respectively. Finally, the docking studies of 9 and 10 were found to be consistent with in vitro TS results. From these studies, compound 9 and 10 has the potential to be developed as TS inhibitors. |
| topic |
2,4-thiazolidinediones 1,3,4-oxadiazoles thymidylate synthase molecular docking pharmacokinetics |
| url |
http://dx.doi.org/10.1080/14756366.2020.1759581 |
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