Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746
Abstract Analogues of chlamydocin derivatives consistently demonstrate multifaceted bioactivities, particularly through HDAC inhibition mechanisms, oncolytic efficacy, and neuronal preservation capacities. These activities primarily originate from their unique cyclic tetrapeptide scaffold and functi...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s13065-025-01581-4 |
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| author | Xiong-En Long Hailiang Xing Yixin He Xuanli Meng Yanling Ma Chang Liu Xi Cao Huiru Nan Min-Jing Cheng Jia-Lei Yan Junyang Liu |
| author_facet | Xiong-En Long Hailiang Xing Yixin He Xuanli Meng Yanling Ma Chang Liu Xi Cao Huiru Nan Min-Jing Cheng Jia-Lei Yan Junyang Liu |
| author_sort | Xiong-En Long |
| collection | DOAJ |
| description | Abstract Analogues of chlamydocin derivatives consistently demonstrate multifaceted bioactivities, particularly through HDAC inhibition mechanisms, oncolytic efficacy, and neuronal preservation capacities. These activities primarily originate from their unique cyclic tetrapeptide scaffold and functional groups within the side chains that enable specific interactions with biomacromolecules. We herein report the total syntheses of three naturally occurring chlamydocin analogues—koshidacin B, TAN-1746, and Ac-TAN-1746. The synthetic strategy employed a modular approach that involved modifying a common intermediate via late-stage olefin cross-metathesis to install the requisite side-chain fragments. This versatile approach enabled an efficient and divergent total synthesis of the target compounds, completing the syntheses in a longest linear sequence of 9–10 steps. Remarkably, TAN-1746 and Ac-TAN-1746 demonstrated significant anti-osteosarcoma activity that exceeded the potency of clinically employed cisplatin—an observation not previously documented. These results strongly validate the utility of the chlamydocin scaffold as a platform for the development of potent inhibitors with promising therapeutic potential. Graphical Abstract |
| format | Article |
| id | doaj-art-b37c21df435d40b19e9afb9f7bbd6342 |
| institution | Kabale University |
| issn | 2661-801X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Chemistry |
| spelling | doaj-art-b37c21df435d40b19e9afb9f7bbd63422025-08-20T03:45:40ZengBMCBMC Chemistry2661-801X2025-07-0119111310.1186/s13065-025-01581-4Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746Xiong-En Long0Hailiang Xing1Yixin He2Xuanli Meng3Yanling Ma4Chang Liu5Xi Cao6Huiru Nan7Min-Jing Cheng8Jia-Lei Yan9Junyang Liu10School of Pharmacy and Food Engineering, Wuyi UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversityCenter for Bioactive Natural Molecules and Innovative Drugs, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan UniversityCenter for Bioactive Natural Molecules and Innovative Drugs, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversityCenter for Bioactive Natural Molecules and Innovative Drugs, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversityCenter for Bioactive Natural Molecules and Innovative Drugs, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversitySchool of Pharmacy and Food Engineering, Wuyi UniversityAbstract Analogues of chlamydocin derivatives consistently demonstrate multifaceted bioactivities, particularly through HDAC inhibition mechanisms, oncolytic efficacy, and neuronal preservation capacities. These activities primarily originate from their unique cyclic tetrapeptide scaffold and functional groups within the side chains that enable specific interactions with biomacromolecules. We herein report the total syntheses of three naturally occurring chlamydocin analogues—koshidacin B, TAN-1746, and Ac-TAN-1746. The synthetic strategy employed a modular approach that involved modifying a common intermediate via late-stage olefin cross-metathesis to install the requisite side-chain fragments. This versatile approach enabled an efficient and divergent total synthesis of the target compounds, completing the syntheses in a longest linear sequence of 9–10 steps. Remarkably, TAN-1746 and Ac-TAN-1746 demonstrated significant anti-osteosarcoma activity that exceeded the potency of clinically employed cisplatin—an observation not previously documented. These results strongly validate the utility of the chlamydocin scaffold as a platform for the development of potent inhibitors with promising therapeutic potential. Graphical Abstracthttps://doi.org/10.1186/s13065-025-01581-4Total synthesisChlamydocin analogKoshidacin BTAN-1746Cross metathesis |
| spellingShingle | Xiong-En Long Hailiang Xing Yixin He Xuanli Meng Yanling Ma Chang Liu Xi Cao Huiru Nan Min-Jing Cheng Jia-Lei Yan Junyang Liu Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 BMC Chemistry Total synthesis Chlamydocin analog Koshidacin B TAN-1746 Cross metathesis |
| title | Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 |
| title_full | Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 |
| title_fullStr | Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 |
| title_full_unstemmed | Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 |
| title_short | Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746 |
| title_sort | total synthesis and biological evaluation of koshidacin b tan 1746 and ac tan 1746 |
| topic | Total synthesis Chlamydocin analog Koshidacin B TAN-1746 Cross metathesis |
| url | https://doi.org/10.1186/s13065-025-01581-4 |
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