Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity
AbstractA series of 21 novel compounds containing a thiosemicarbazone moiety were designed and synthesised based on hit compound 1 from our in-house compound library screening. Most compounds showed potent antifungal activity in vitro against seven common pathogenic fungi. Notably, all compounds sho...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2202362 |
| _version_ | 1797400970984947712 |
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| author | Xianru Li Liping Li Haonan Zhang Xiaochen Chi Yuanying Jiang Tingjunhong Ni |
| author_facet | Xianru Li Liping Li Haonan Zhang Xiaochen Chi Yuanying Jiang Tingjunhong Ni |
| author_sort | Xianru Li |
| collection | DOAJ |
| description | AbstractA series of 21 novel compounds containing a thiosemicarbazone moiety were designed and synthesised based on hit compound 1 from our in-house compound library screening. Most compounds showed potent antifungal activity in vitro against seven common pathogenic fungi. Notably, all compounds showed high potency against Candida glabrata 537 (MIC = ≤0.0156-2 µg/mL). Of note, compounds 5j and 5r displayed excellent antifungal activity against Candida krusei 4946 and Candida auris 922. Additionally, compounds 5j and 5r also showed high potency against 15 C. glabrata isolates with MIC values ranging from 0.0625 µg/mL to 4 µg/mL, with compound 5r being slightly superior to 5j. Moreover, compound 5r has certain effect against biofilm formation of C. glabrata. Furthermore, compound 5r has minimal cytotoxicity against HUVECs with an IC50 value of 15.89 µg/mL and no haemolysis at 64 µg/mL. Taken together, these results suggest that promising lead compound 5r deserves further investigation. |
| first_indexed | 2024-03-09T02:03:10Z |
| format | Article |
| id | doaj.art-c3efca1705544669a7dec44a5d903c1c |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:03:10Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c3efca1705544669a7dec44a5d903c1c2023-12-08T03:24:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2202362Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activityXianru Li0Liping Li1Haonan Zhang2Xiaochen Chi3Yuanying Jiang4Tingjunhong Ni5Department of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of General Surgery, General Hospital of Ningxia Medical University, Yinchuan City, Ningxia Hui Autonomous Region, ChinaSchool of Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaAbstractA series of 21 novel compounds containing a thiosemicarbazone moiety were designed and synthesised based on hit compound 1 from our in-house compound library screening. Most compounds showed potent antifungal activity in vitro against seven common pathogenic fungi. Notably, all compounds showed high potency against Candida glabrata 537 (MIC = ≤0.0156-2 µg/mL). Of note, compounds 5j and 5r displayed excellent antifungal activity against Candida krusei 4946 and Candida auris 922. Additionally, compounds 5j and 5r also showed high potency against 15 C. glabrata isolates with MIC values ranging from 0.0625 µg/mL to 4 µg/mL, with compound 5r being slightly superior to 5j. Moreover, compound 5r has certain effect against biofilm formation of C. glabrata. Furthermore, compound 5r has minimal cytotoxicity against HUVECs with an IC50 value of 15.89 µg/mL and no haemolysis at 64 µg/mL. Taken together, these results suggest that promising lead compound 5r deserves further investigation.https://www.tandfonline.com/doi/10.1080/14756366.2023.2202362Hydroxy-phenylhydrazonethiosemicarbazoneantifungalstructure-activity relationshipsynthesis |
| spellingShingle | Xianru Li Liping Li Haonan Zhang Xiaochen Chi Yuanying Jiang Tingjunhong Ni Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity Journal of Enzyme Inhibition and Medicinal Chemistry Hydroxy-phenylhydrazone thiosemicarbazone antifungal structure-activity relationship synthesis |
| title | Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity |
| title_full | Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity |
| title_fullStr | Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity |
| title_full_unstemmed | Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity |
| title_short | Discovery of novel thiosemicarbazone derivatives with potent and selective anti-Candida glabrata activity |
| title_sort | discovery of novel thiosemicarbazone derivatives with potent and selective anti candida glabrata activity |
| topic | Hydroxy-phenylhydrazone thiosemicarbazone antifungal structure-activity relationship synthesis |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2202362 |
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