{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:47Z","timestamp":1787028467746,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008306","name":"University of Wroc\u0142aw","doi-asserted-by":"publisher","award":["PL8960005408"],"award-info":[{"award-number":["PL8960005408"]}],"id":[{"id":"10.13039\/501100008306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malaria is still one of the most dangerous infectious diseases and the emergence of drug resistant parasites only worsens the situation. A series of new tetrahydro-\u03b2-carbolines were designed, synthesized by the Pictet\u2013Spengler reaction, and characterized. Further, the compounds were screened for their in vitro antiplasmodial activity against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Moreover, molecular modeling studies were performed to assess the potential action of the designed molecules and toxicity assays were conducted on the human microvascular endothelial (HMEC-1) cell line and human red blood cells. Our studies identified N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) (a mixture of diastereomers) as the most promising compound endowed with the highest antiplasmodial activity, highest selectivity, and lack of cytotoxicity. In silico simulations carried out for (1S,3R)-7 provided useful insights into its possible interactions with enzymes essential for parasite metabolism. Further studies are underway to develop the optimal nanosized lipid-based delivery system for this compound and to determine its precise mechanism of action.<\/jats:p>","DOI":"10.3390\/ijms222413569","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synthesis, Molecular Docking and Antiplasmodial Activities of New Tetrahydro-\u03b2-Carbolines"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-8007","authenticated-orcid":false,"given":"Anna","family":"Jaromin","sequence":"first","affiliation":[{"name":"Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroc\u0142aw, Joliot-Curie 14a, 50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Gryz\u0142o","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Jamrozik","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-8892","authenticated-orcid":false,"given":"Silvia","family":"Parapini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche per la Salute, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-1066","authenticated-orcid":false,"given":"Nicoletta","family":"Basilico","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Ceg\u0142a","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5108-4492","authenticated-orcid":false,"given":"Donatella","family":"Taramelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2510-7237","authenticated-orcid":false,"given":"Agnieszka","family":"Zag\u00f3rska","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"ref_1","unstructured":"(2021, October 11). 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