{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T04:52:09Z","timestamp":1768625529772,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["UIP-2017-05-5160"],"award-info":[{"award-number":["UIP-2017-05-5160"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union from the European Social Fund","award":["UIP-2017-05-5160"],"award-info":[{"award-number":["UIP-2017-05-5160"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine\/\u03b2-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the \u03b2-carboline ring and ferrocene, as well as its position on the \u03b2-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI &gt; 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2\/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.<\/jats:p>","DOI":"10.3390\/ijms23169315","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T21:39:21Z","timestamp":1660858761000},"page":"9315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity"],"prefix":"10.3390","volume":"23","author":[{"given":"Goran","family":"Poje","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Marinovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-6340","authenticated-orcid":false,"given":"Kristina","family":"Pavi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Mio\u010d","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruder Bo\u0161kovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-2722","authenticated-orcid":false,"given":"Marijeta","family":"Kralj","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruder Bo\u0161kovic Institute, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lais Pessanha","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-1429","authenticated-orcid":false,"given":"Jana","family":"Held","sequence":"additional","affiliation":[{"name":"Institute of Tropical Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Perkovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-1116","authenticated-orcid":false,"given":"Zrinka","family":"Raji\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"key":"ref_1","unstructured":"(2022, July 20). 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