Synthesis of α-Santonin Derivatives Linked to N-, S-, and O-Heterocycles via 1,2,3-Triazole-Linker Investigation of Antimicrobial Effects /
Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this go...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2026
|
| Sorozat: | ANTIBIOTICS
15 No. 6 |
| Tárgyszavak: | |
| doi: | 10.3390/antibiotics15060611 |
| mtmt: | 37340023 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/40464 |
| Tartalmi kivonat: | Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available α-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN3/AcOH/Et3N system at its highly reactive α-methylene-γ-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene–heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 µg/mL conc.), C. krusei (up to 51% inhibition at 10 µg/mL conc.) and C. albicans (up to 52% inhibition at 10 µg/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents. |
|---|---|
| Terjedelem/Fizikai jellemzők: | 16 |
| ISSN: | 2079-6382 |