{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T20:43:40Z","timestamp":1772311420858,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU","award":["CQ\/UM (UID\/QUI\/00686\/2020)"],"award-info":[{"award-number":["CQ\/UM (UID\/QUI\/00686\/2020)"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU","award":["CEECINST\/00156\/2018\/CP1642\/CT0011"],"award-info":[{"award-number":["CEECINST\/00156\/2018\/CP1642\/CT0011"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU","award":["SFRH\/BD\/05278\/2020"],"award-info":[{"award-number":["SFRH\/BD\/05278\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia (FCT) and FEDER (European Fund for Regional Development)-COMPETE-QRENEU","award":["REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["REDE\/1517\/RMN\/2005"]}]},{"name":"PhD","award":["CQ\/UM (UID\/QUI\/00686\/2020)"],"award-info":[{"award-number":["CQ\/UM (UID\/QUI\/00686\/2020)"]}]},{"name":"PhD","award":["CEECINST\/00156\/2018\/CP1642\/CT0011"],"award-info":[{"award-number":["CEECINST\/00156\/2018\/CP1642\/CT0011"]}]},{"name":"PhD","award":["SFRH\/BD\/05278\/2020"],"award-info":[{"award-number":["SFRH\/BD\/05278\/2020"]}]},{"name":"PhD","award":["REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["REDE\/1517\/RMN\/2005"]}]},{"name":"POCI 2010 (FEDER) and FCT","award":["CQ\/UM (UID\/QUI\/00686\/2020)"],"award-info":[{"award-number":["CQ\/UM (UID\/QUI\/00686\/2020)"]}]},{"name":"POCI 2010 (FEDER) and FCT","award":["CEECINST\/00156\/2018\/CP1642\/CT0011"],"award-info":[{"award-number":["CEECINST\/00156\/2018\/CP1642\/CT0011"]}]},{"name":"POCI 2010 (FEDER) and FCT","award":["SFRH\/BD\/05278\/2020"],"award-info":[{"award-number":["SFRH\/BD\/05278\/2020"]}]},{"name":"POCI 2010 (FEDER) and FCT","award":["REDE\/1517\/RMN\/2005"],"award-info":[{"award-number":["REDE\/1517\/RMN\/2005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leishmaniasis and Human African trypanosomiasis pose significant public health threats in resource-limited regions, accentuated by the drawbacks of the current antiprotozoal treatments and the lack of approved vaccines. Considering the demand for novel therapeutic drugs, a series of BODIPY derivatives with several functionalizations at the meso, 2 and\/or 6 positions of the core were synthesized and characterized. The in vitro activity against Trypanosoma brucei and Leishmania major parasites was carried out alongside a human healthy cell line (MRC-5) to establish selectivity indices (SIs). Notably, the meso-substituted BODIPY, with 1-dimethylaminonaphthalene (1b) and anthracene moiety (1c), were the most active against L. major, displaying IC50 = 4.84 and 5.41 \u03bcM, with a 16 and 18-fold selectivity over MRC-5 cells, respectively. In contrast, the mono-formylated analogues 2b and 2c exhibited the highest toxicity (IC50 = 2.84 and 6.17 \u03bcM, respectively) and selectivity (SI = 24 and 11, respectively) against T. brucei. Further insights on the activity of these compounds were gathered from molecular docking studies. The results suggest that these BODIPYs act as competitive inhibitors targeting the NADPH\/NADP+ linkage site of the pteridine reductase (PR) enzyme. Additionally, these findings unveil a range of quasi-degenerate binding complexes formed between the PRs and the investigated BODIPY derivatives. These results suggest a potential correlation between the anti-parasitic activity and the presence of multiple configurations that block the same site of the enzyme.<\/jats:p>","DOI":"10.3390\/molecules29092072","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T08:14:31Z","timestamp":1714464871000},"page":"2072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Designing Antitrypanosomal and Antileishmanial BODIPY Derivatives: A Computational and In Vitro Assessment"],"prefix":"10.3390","volume":"29","author":[{"given":"Raquel C. R.","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"Advanced (Magnetic) Theranostic Nanostructures Lab, International Iberian Nanotechnology Laboratory, Av. Mestre Jos\u00e9 Veiga s\/n, 4715-330 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-0086","authenticated-orcid":false,"given":"Filipe","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-282X","authenticated-orcid":false,"given":"Pablo","family":"Pe\u00f1alver","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez Neyra, CSIC, PTS Granada, Avenida del Conocimiento, 17, 18016 Armilla, Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-4720","authenticated-orcid":false,"given":"Susana P. G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-405X","authenticated-orcid":false,"given":"Juan C.","family":"Morales","sequence":"additional","affiliation":[{"name":"Instituto de Parasitolog\u00eda y Biomedicina L\u00f3pez Neyra, CSIC, PTS Granada, Avenida del Conocimiento, 17, 18016 Armilla, Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-1626","authenticated-orcid":false,"given":"M. Manuela M.","family":"Raposo","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41579-022-00777-y","article-title":"Anti-Trypanosomatid Drug Discovery: Progress and Challenges","volume":"21","author":"Wyllie","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, R.C.R., Pe\u00f1alver, P., Costa, S.P.G., Morales, J.C., and Raposo, M.M.M. (2023). Polyaromatic Bis(Indolyl)Methane Derivatives with Antiproliferative and Antiparasitic Activity. Molecules, 28.","DOI":"10.3390\/molecules28237728"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kourbeli, V., Chontzopoulou, E., Moschovou, K., Pavlos, D., Mavromoustakos, T., and Papanastasiou, I.P. (2021). 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