{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:17:50Z","timestamp":1787818670364,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018818","name":"Hungarian Research Foundation","doi-asserted-by":"publisher","award":["K-138871"],"award-info":[{"award-number":["K-138871"]}],"id":[{"id":"10.13039\/501100018818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015498","name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","doi-asserted-by":"publisher","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"10.13039\/501100015498","id-type":"DOI","asserted-by":"publisher"}]},{"award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"https:\/\/ror.org\/03vhmm238","id-type":"ROR","asserted-by":"publisher"}]},{"name":"TKP2021-EGA funding scheme"},{"name":"EK\u00d6P-191-SZTE"},{"name":"University of Szeged Open Access Fund","award":["8678"],"award-info":[{"award-number":["8678"]}]},{"award":["8678"],"award-info":[{"award-number":["8678"]}],"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>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 \u03b1-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 \u03b1-methylene-\u03b3-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\u2013heterocycle 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 \u00b5g\/mL conc.), C. krusei (up to 51% inhibition at 10 \u00b5g\/mL conc.) and C. albicans (up to 52% inhibition at 10 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/antibiotics15060611","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:27:21Z","timestamp":1781666841000},"page":"611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis of \u03b1-Santonin Derivatives Linked to N-, S-, and O-Heterocycles via 1,2,3-Triazole-Linker: Investigation of Antimicrobial Effects"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7938-484X","authenticated-orcid":false,"given":"M\u00e1ria Fanni","family":"Boncz","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7929-5806","authenticated-orcid":false,"given":"Kitti","family":"Tari","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1651-4623","authenticated-orcid":false,"given":"Andr\u00e1s","family":"Szekeres","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1na","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-5300","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Zupk\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmacodynamics and Biopharmacy, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8296-887X","authenticated-orcid":false,"given":"Tam Minh","family":"Le","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"},{"name":"HUN-REN-SZTE Stereochemistry Research Group, Hungarian Research Network, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-8409","authenticated-orcid":false,"given":"Zsolt","family":"Szakonyi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, University of Szeged, E\u00f6tv\u00f6s utca 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100947","DOI":"10.1016\/j.lanmic.2024.07.010","article-title":"Antimicrobial Resistance: A Concise Update","volume":"6","author":"Ho","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100081","DOI":"10.1016\/j.glmedi.2024.100081","article-title":"Antimicrobial Resistance: Impacts, Challenges, and Future Prospects","volume":"2","author":"Ahmed","year":"2024","journal-title":"J. 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