{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:01:31Z","timestamp":1777039291309,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide\u2013alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a\u2013h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 \u00b5M, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 \u00b5M. Density functional calculations at the B3LYP\/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide\u2013alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal\/mol and 29.35 kcal\/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.<\/jats:p>","DOI":"10.3390\/molecules27030769","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:40:18Z","timestamp":1643143218000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation"],"prefix":"10.3390","volume":"27","author":[{"given":"Ali","family":"Oubella","sequence":"first","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdoullah","family":"Bimoussa","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdellah","family":"N\u2019ait Oussidi","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mourad","family":"Fawzi","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aziz","family":"Auhmani","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Morjani","sequence":"additional","affiliation":[{"name":"BioSpectroscopie Translationnelle, BioSpecT\u2014EA7506, UFR de Pharmacie, Universit\u00e9 de Reims Champagne-Ardenne, 51 Rue Cognacq Jay, CEDEX, 51096 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelkhalek","family":"Riahi","sequence":"additional","affiliation":[{"name":"Equipe MSO, CNRS UMR 7312 Institut de Chimie Mol\u00e9culaire, Universit\u00e9 de Reims Champagne-Ardenne, Bat. Europol\u2019Agro-Moulin de La Housse UFR Sciences B.P., 1039, CEDEX 2, 51687 Reims, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u2019hamed","family":"Esseffar","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Parish","sequence":"additional","affiliation":[{"name":"Gottwald Science Center, 28Westhampton Way, University of Richmond, Richmond, VA 23173, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1876-7544","authenticated-orcid":false,"given":"Moulay Youssef","family":"Ait Itto","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie Mol\u00e9culaire, D\u00e9partement de Chimie, Facult\u00e9 des Sciences, Semlalia B.P 2390, Marrakech 40001, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ejmech.2012.06.001","article-title":"Anthranilic Acid-Based Diamides Derivatives Incorporating Aryl-Isoxazoline Pharmacophore as Potential Anticancer Agents: Design, Synthesis and Biological Evaluation","volume":"54","author":"Liqiao","year":"2012","journal-title":"Eur. 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