Project's information
| Project's title | Semisynthesis of artemisinin-oxadiazole derivatives and investigation of their biological activities |
| Project’s code | KHCBHH.02/21-23 |
| Research hosting institution | Institute of Chemistry |
| Project leader’s name | Dr. Tran Duc Quan |
| Project duration | 01/01/2021 - 31/12/2023 |
| Project’s budget | 1,500 million VND |
| Classify | Grade B |
| Goal and objectives of the project | Semi-synthetic research of biologically active artemisinin-oxadiazole derivatives. |
| Main results | - From artemisinin and 3-methyl cyanobenzoate, through multi-steps procedures, 36 intermediate compounds have been synthesized as raw materials for the synthesis of artemisinin-oxadiazole.
- These intermediate compounds (including fifteen artemisinin derivates; nine 1,2,4-oxadiazole compounds, and eight 1,3,4-oxadiazole compounds) are known compounds but not available in the market.
- For the first time, 9 artemisinin-1,2,4-oxadiazole derivatives (36a-i) and 8 artemisinin-1,3,4-oxadiazole derivatives (37a-h) were successfully synthesized.
- The synthesis of artemisinin-oxadiazole derivatives was carried out under mild, environmentally friendly conditions with good yields.
- A set of spectral profiles (including 1H-NMR spectrum, 13C-NMR spectrum and HRMS spectrum) has been measured and analyzed to elucidate the structure of 17 artemisinin-oxadiazole derivatives (36a-i; 37a-h).
- The cytotoxic activity of the prepared artemisin-1,2,4-oxadiazole derivatives (36a-i) against HepG2 and MCF-7 cell lines was screened and investigated.
- The compounds artemisin-1,3,4-oxadiazole (37a-h) were tested for cytotoxic activity against HepG2 and LU-1 cell lines.
- The results showed that artemisin-oxadiazole derivatives all exhibited cytotoxic activity. Among them, many derivatives had much more potent activity than DHA precursor and were comparable to Ellipticine
- Results of the antimalarial activity of three artemisin-oxadiazole derivatives (36f, 37f, and 37g) against malarial parasite P. falciparum. indicated that all 3 tested artemisinin-oxadiazole derivatives had potent activity against both on both drug-resistant (K1) and non-drug-resistant (T96) strains. Accordingly, the activity of 2 derivatives 37f and 37g was ten-fold higher than that of the derivative 36f. |
| Novelty and actuality and scientific meaningfulness of the results | - For the first time, 17 new derivatives of artemisinin including nine derivatives with 1,2,4-oxadiazoles(36a-i ) and eight derivatives with 1,3,4-oxadiazols (37a-h) have been synthesized and structurally determined.
- For the first time, the cytotoxic activity of artemisinin-oxadiazole derivatives has been reported. The prepared derivatives of artemisinin showed potent cytotoxic activity and are potential candidates for futher investigations in drug development of new anticancer agents.
- Contributing to expanding the applicability of artemisinin and its derivatives in the fields of medicine and pharmacy. |
| Products of the project | + Scientific papers in referred journals (list):
- Synthesis and cytotoxic activity evaluation of novel dihydroartemisinin and zerumbone conjugates with 2-mercapto-1,3,4-oxadiazoles as potential EGFR inhibitors. Journal of Chemical Research
- Dihydroartemisinin and zerumbone esters of ataluren and its analogs as anticancer agents and EGFR inhibitors. Journal of Chemical Research
+ Patents (list):
- Dihydroartemisinin esters of ataluren and its analogs as anticancer agents and EGFR inhibitors. |
| Recommendations | From the achieved results, the research team would like to propose the Institute of Chemistry and the Vietnam Academy of Science and Technology to enable and support the research team to continue developing the research results in the future grants with purpose of developing and finding new anticancer drugs based on the artemisinin-oxadiazole derivatives, because the obtained derivatives of artemisinin in the project exhibited a very promising cytotoxic activity against different anti-cancer cell lines. |
| Images of project |
|
