{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:20Z","timestamp":1785415520758,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-23-00810"],"award-info":[{"award-number":["25-23-00810"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-23-00810"],"award-info":[{"award-number":["25-23-00810"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, a simple and efficient method for the synthesis of conjugates of N-acyl derivatives of 3,5-bis(benzylidene)-4-piperidones and phenothiazine was developed. The method was based on the acylation of 3,5-bis(benzylidene)-4-piperidones with chloroacetic acid chloride, followed by treatment of the product with sodium azide and an azide-alkyne [3+2] cycloaddition reaction between the resulting azide and 10-(prop-2-yn-1-yl)-10H-phenothiazine in the final step. Using this method, a series of seven compounds 23\u201329 were synthesized. The structure of synthesized compounds 23\u201329 was studied using 1H, 13C, and 19F NMR spectroscopy and ESI-MS mass spectrometry. The cytotoxicity of compounds 23\u201329 and their hydrochloride salts 30\u201336 towards pancreatic adenocarcinoma Panc-1, bladder cancer T-24, glioblastoma T98G, breast adenocarcinoma BT-20, and normal dermal fibroblast DF-1 cells was studied using an MTT assay. Compound 29, containing 3,4,5-trimethoxyl radicals at the aromatic ring, and its hydrochloride salt 36, demonstrated the best cytotoxicity against Panc-1, T-24, T98G, and BT-20 cancer cells. Hydrochloride salts were found to exhibit superior cytotoxicity against Panc-1, T-24, T98G, and BT-20 cancer cells compared to the original 3,5-bis(benzylidene)-4-piperidones and free bases. Selective cytotoxic action against Panc-1, T-24, T98G, and BT-20 cancer cells compared to normal DF-1 cells was also observed for all the obtained compounds and their salts.<\/jats:p>","DOI":"10.3390\/ijms27094104","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:57:29Z","timestamp":1777967849000},"page":"4104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Cytotoxic Activity Study of Conjugates of N-Acyl Derivatives of 3,5-Bis(benzylidene)-4-piperidones and Phenothiazine"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8562-4696","authenticated-orcid":false,"given":"Pavel","family":"Yudaev","sequence":"first","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-3370","authenticated-orcid":false,"given":"Yulia","family":"Aleksandrova","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7086-6563","authenticated-orcid":false,"given":"Inna","family":"Shagina","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Artyushin","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sharova","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9227-7434","authenticated-orcid":false,"given":"Alexey","family":"Rodionov","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9346-5920","authenticated-orcid":false,"given":"Margarita","family":"Neganova","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Brel","sequence":"additional","affiliation":[{"name":"Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova St., 28, Bld. 1, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1007\/s11101-024-09940-0","article-title":"Recent advancements in natural compounds for cancer therapy and prevention","volume":"23","author":"Pavithra","year":"2024","journal-title":"Phytochem. 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