{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:30:18Z","timestamp":1788982218632,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["107270 (S.D.K.); 190403426633 (J.DLM.)"],"award-info":[{"award-number":["107270 (S.D.K.); 190403426633 (J.DLM.)"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa","award":["98566 (A.L.E.)"],"award-info":[{"award-number":["98566 (A.L.E.)"]}]},{"name":"National Research Foundation CPRR","award":["105829 (A.L.E.)"],"award-info":[{"award-number":["105829 (A.L.E.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 P. falciparum) over the investigated trypanosomiasis causal agent (T. b. brucei 427) with mostly single digit micromolar IC50 values. When read in tandem with the biological performance of previously reported structurally similar non-coumarin, phenyl derivatives (i.e., ferrocenyl 1,3-benzoxazines and \u03b1-aminocresols), structure-activity relationship analyses suggest that the presence of the coumarin nucleus is tolerated for biological activity though this may lead to reduced efficacy. Preliminary mechanistic studies with the most promising compound (11b) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects.<\/jats:p>","DOI":"10.3390\/molecules26051333","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T10:36:37Z","timestamp":1614681397000},"page":"1333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-6801","authenticated-orcid":false,"given":"Mziyanda","family":"Mbaba","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3041-2861","authenticated-orcid":false,"given":"Laura M. K.","family":"Dingle","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Biomedical Biotechnology Research Unit, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9036-5588","authenticated-orcid":false,"given":"Ayanda I.","family":"Zulu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-0999","authenticated-orcid":false,"given":"Dustin","family":"Laming","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarryn","family":"Swart","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Anne","family":"de la Mare","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Biomedical Biotechnology Research Unit, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4409-1955","authenticated-orcid":false,"given":"Heinrich C.","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3615-6651","authenticated-orcid":false,"given":"Adrienne L.","family":"Edkins","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Biomedical Biotechnology Research Unit, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0725-5738","authenticated-orcid":false,"given":"Setshaba D.","family":"Khanye","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa"},{"name":"Centre for Chemico- and Biomedicinal Research, Rhodes University, Makhanda 6140, South Africa"},{"name":"Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1098\/rspb.2000.1290","article-title":"Species concepts and malaria parasites: Detecting a cryptic species of Plasmodium","volume":"267","author":"Perkins","year":"2000","journal-title":"Proc. R. Soc. B"},{"key":"ref_2","unstructured":"World Health Organization Malaria. Available online: https:\/\/www.who.int\/health-topics\/malaria#tab=tab_1."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Smith, T.K., Bringaud, F., Nolan, D.P., and Figueiredo, L.M. (2017). Metabolic reprogramming during the Trypanosoma brucei life cycle. F1000Research, 6.","DOI":"10.12688\/f1000research.10342.1"},{"key":"ref_4","unstructured":"Medicines for Malaria Venture (2020, August 20). The Pathogen Box. Available online: https:\/\/www.mmv.org\/mmv-open\/pathogen-box."},{"key":"ref_5","unstructured":"(2020, October 31). Drugs for Neglected Disease Initiative (NDDi). Available online: https:\/\/dndi.org\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4269\/ajtmh.2007.77.181","article-title":"Artemisinin-based combination treatment of falciparum malaria","volume":"77","author":"Nosten","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_7","unstructured":"World Health Organization WHO Status Reports on Artemisinin Resistance and ACT Efficacy. Available online: https:\/\/www.who.int\/malaria\/areas\/drug_resistance\/updates\/en\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41570-017-0066","article-title":"The medicinal chemistry of ferrocene and its derivatives","volume":"1","author":"Patra","year":"2017","journal-title":"Nat. Rev. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1039\/C8DT03440K","article-title":"Ferrocene-appended pharmacophores: An exciting approach for modulating the biological potential of organic scaffolds","volume":"48","author":"Singh","year":"2019","journal-title":"Dalton Trans."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111791","DOI":"10.1016\/j.ejmech.2019.111791","article-title":"Current scenario of ferrocene-containing hybrids for antimalarial activity","volume":"185","author":"Xiao","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1039\/b004291i","article-title":"Solvation descriptors for ferrocene, and the estimation of some physicochemical and biochemical properties","volume":"24","author":"Abraham","year":"2000","journal-title":"New J. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/ejic.201600983","article-title":"Why is ferrocene so exceptional?","volume":"2017","author":"Astruc","year":"2017","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1021\/jm970401y","article-title":"Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene\u2212 chloroquine analogue","volume":"40","author":"Biot","year":"1997","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Top, S., Tang, J., Vessi\u00e8res, A., Carrez, D., Provot, C., and Jaouen, G. (1996). Ferrocenyl hydroxytamoxifen: A prototype for a new range of oestradiol receptor site-directed cytotoxics. Chem. Commun., 955\u2013956.","DOI":"10.1039\/CC9960000955"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1039\/c2dt30700f","article-title":"Ferrocenyl catechols: Synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells","volume":"41","author":"Tan","year":"2012","journal-title":"Dalton Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1039\/C5CS00486A","article-title":"Ferrocifen type anti cancer drugs","volume":"44","author":"Jaouen","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1007\/s00044-013-0748-4","article-title":"Synthesis, in vitro antiplasmodial and antiproliferative activities of a series of quinoline\u2013ferrocene hybrids","volume":"23","author":"Smith","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4345","DOI":"10.1021\/om500622p","article-title":"Synthesis and evaluation of a carbosilane congener of ferroquine and its corresponding half-sandwich ruthenium and rhodium complexes for antiplasmodial and \u03b2-hematin inhibition activity","volume":"33","author":"Li","year":"2014","journal-title":"Organometallics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejmech.2019.06.023","article-title":"Ferroquine-derived polyamines that target resistant Plasmodium falciparum","volume":"179","author":"Stringer","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111963","DOI":"10.1016\/j.ejmech.2019.111963","article-title":"Design and synthesis of novel ferrocene-quinoline conjugates and evaluation of their electrochemical and antiplasmodium properties","volume":"187","author":"Combrinck","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.jorganchem.2010.11.021","article-title":"Ferrocene\u2013indole hybrids for cancer and malaria therapy","volume":"696","author":"Quirante","year":"2011","journal-title":"J. Organomet. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.poly.2014.03.006","article-title":"Synthesis, spectral characterization, cytotoxicity and enzyme-inhibiting activity of new ferrocene\u2013indole hybrids","volume":"80","year":"2014","journal-title":"Polyhedron"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/aoc.3452","article-title":"Ferrocene-substituted 3, 3\u2032-diindolylmethanes with improved anticancer activity","volume":"30","author":"Muenzner","year":"2016","journal-title":"Appl. Organomet. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.inoche.2013.06.019","article-title":"Organometallic benzimidazoles: Synthesis, characterization and antimalarial activity","volume":"35","author":"Toro","year":"2013","journal-title":"Inorg. Chem. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126918","DOI":"10.1016\/j.molstruc.2019.126918","article-title":"Exploring DNA-Binding and anticancer properties of benzoimidazolyl-ferrocene dye","volume":"1198","author":"Babgi","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bmcl.2017.12.057","article-title":"Synthesis, in vitro antimalarial activities and cytotoxicities of amino-artemisinin-ferrocene derivatives","volume":"28","author":"Coertzen","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1016\/j.bmcl.2018.08.037","article-title":"Synthesis, antimalarial activities and cytotoxicities of amino-artemisinin-1, 2-disubstituted ferrocene hybrids","volume":"28","author":"Coertzen","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ejmech.2015.04.053","article-title":"New efficient artemisinin derived agents against human leukemia cells, human cytomegalovirus and Plasmodium falciparum: 2nd generation 1, 2, 4-trioxane-ferrocene hybrids","volume":"97","author":"Reiter","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.2174\/1381612043382693","article-title":"Studies on coumarins and coumarin-related compounds to determine their therapeutic role in the treatment of cancer","volume":"10","author":"Lacy","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/B978-0-12-817903-1.00003-6","article-title":"Anticancer activity of natural coumarins for biological targets","volume":"64","year":"2020","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1016\/j.bmcl.2012.04.100","article-title":"Coumarin\u2013trioxane hybrids: Synthesis and evaluation as a new class of antimalarial scaffolds","volume":"22","author":"Sashidhara","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114","DOI":"10.2174\/1568026618666171215101158","article-title":"Recent development of coumarin derivatives as potential antiplasmodial and antimalarial agents","volume":"18","author":"Hu","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5569","DOI":"10.1016\/j.bmcl.2012.07.013","article-title":"Antitrypanosomal and antioxidant properties of 4-hydroxycoumarins derivatives","volume":"22","author":"Serra","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, G.A., Cerecetto, H., Poser, G., Canto, R.F.S., and Eifler-Lima, V.L. (2020). Chagas disease and coumarins: A review of natural and synthetic coumarins as anti-Trypanosoma cruzi agents. Mini-Rev. Med. Chem.","DOI":"10.2174\/1389557521666201229125931"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112514","DOI":"10.1016\/j.ejmech.2020.112514","article-title":"Natural and synthetic coumarins as antileishmanial agents: A review","volume":"203","author":"Spillere","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mandlik, V., Patil, S., Bopanna, R., Basu, S., and Singh, S. (2016). Biological activity of coumarin derivatives as anti-leishmanial agents. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164585"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ejmech.2015.06.017","article-title":"Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents","volume":"100","author":"Keri","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejmech.2017.05.004","article-title":"Recent developments of coumarin-containing derivatives and their anti-tubercular activity","volume":"136","author":"Hu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jinorgbio.2017.04.014","article-title":"Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity","volume":"172","author":"Mbaba","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00775-018-1634-9","article-title":"Novobiocin\u2013ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition","volume":"24","author":"Mbaba","year":"2019","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.6023\/cjoc201611036","article-title":"Synthesis and Properties of 4-Ferrocenyl-carboxybenzene-coumarin Derivatives","volume":"37","author":"Biao","year":"2017","journal-title":"Chin. J. Org. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120968","DOI":"10.1016\/j.jorganchem.2019.120968","article-title":"Synthesis, characterization and antitumor activity of novel ferrocene-coumarin conjugates","volume":"902","author":"Wei","year":"2019","journal-title":"J. Organomet. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.polymer.2012.01.052","article-title":"Preparation of novel benzoxazine monomers containing ferrocene moiety and properties of polybenzoxazines","volume":"53","author":"Li","year":"2012","journal-title":"Polymer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4909","DOI":"10.1016\/j.polymer.2013.06.056","article-title":"A novel thermal-resistant copolymer from polysiloxane-based polybenzoxazine precursor and ferrocene-based benzoxazine monomer","volume":"54","author":"Li","year":"2013","journal-title":"Polymer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.reactfunctpolym.2017.06.009","article-title":"Adapting benzoxazine chemistry for unconventional applications","volume":"129","author":"Kiskan","year":"2018","journal-title":"React. Funct. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111924","DOI":"10.1016\/j.ejmech.2019.111924","article-title":"Repurposing a polymer precursor: Synthesis and in vitro medicinal potential of ferrocenyl 1, 3-benzoxazine derivatives","volume":"187","author":"Mbaba","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1002\/cbic.202000132","article-title":"The in vitro antiplasmodial and antiproliferative activity of new ferrocene-based \u03b1-aminocresols targeting hemozoin inhibition and DNA interaction","volume":"21","author":"Mbaba","year":"2020","journal-title":"ChemBioChem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2725(08)60840-5","article-title":"1, 3-Oxazine Derivatives","volume":"Volume 23","author":"Eckstein","year":"1979","journal-title":"Advances in Heterocyclic Chemistry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/187426a0","article-title":"Anti-neoplastic activity of tetrahydro-1, 3-oxazine derivatives","volume":"187","author":"Mordarska","year":"1960","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lohar, T., Mane, A., Kamat, S., and Salunkhe, R. (2018). A versatile water-stable fluorine containing organometallic lewis acid used in green synthesis of 1, 3-oxazine scaffolds at room temperature. Polycycl. Aromat. Compd., 1\u201313.","DOI":"10.1080\/10406638.2018.1538057"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1007\/s10593-013-1209-1","article-title":"Synthesis and structure of Schiff bases derived from 3-formyl-4-hydroxycoumarin and diamines","volume":"48","author":"Milevskii","year":"2013","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1016\/j.tet.2015.03.025","article-title":"One-step synthesis of furocoumarins via oxidative annulation of 4-hydroxycoumarins with DDQ","volume":"71","author":"Li","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1081\/SCC-100104003","article-title":"A convenient one-pot synthesis of 4-hydroxycoumarin, 4-hydroxythiocoumarin, and 4-hydroxyquinolin-2 (1 H)-one","volume":"31","author":"Jung","year":"2001","journal-title":"Synth. Commun."},{"key":"ref_54","first-page":"817","article-title":"A route to the synthesis of novel coumarins","volume":"135","author":"Mohseni","year":"2004","journal-title":"Monatsh. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1021\/jo960057x","article-title":"Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. studies on direct and indirect reductive amination procedures1","volume":"61","author":"Carson","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1139\/v97-043","article-title":"Keto\u2013enol tautomerism, NMR spectra, and H\u2013D exchange of 4-hydroxycoumarins","volume":"75","author":"Traven","year":"1997","journal-title":"Can. J. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8179","DOI":"10.1021\/acs.jpca.9b05065","article-title":"Benzoxazine formation mechanism evaluation by direct observation of reaction intermediates","volume":"123","author":"Ribeiro","year":"2019","journal-title":"J. Phys. Chem. A"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1016\/S0040-4039(01)00991-1","article-title":"Preparation of carbamates from amines and alcohols under mild conditions","volume":"42","author":"Bochet","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10387","DOI":"10.1021\/jm300831b","article-title":"Mimicking the intramolecular hydrogen bond: Synthesis, biological evaluation, and molecular modeling of benzoxazines and quinazolines as potential antimalarial agents","volume":"55","author":"Gemma","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ab.2004.11.022","article-title":"A colorimetric high-throughput \u03b2-hematin inhibition screening assay for use in the search for antimalarial compounds","volume":"338","author":"Ncokazi","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ejmech.2013.03.072","article-title":"Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2, 11-disubstituted indolo [2, 3-b] quinolines","volume":"64","author":"Lu","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jphotobiol.2013.03.013","article-title":"Drug\u2013DNA interactions and their study by UV\u2013Visible, fluorescence spectroscopies and cyclic voltametry","volume":"124","author":"Sirajuddin","year":"2013","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jphotobiol.2012.03.012","article-title":"Study of DNA\u2013emodin interaction by FTIR and UV\u2013vis spectroscopy","volume":"111","author":"Saito","year":"2012","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.saa.2012.05.045","article-title":"Spectroscopic studies on the interaction of calf thymus DNA with the drug levetiracetam","volume":"96","author":"Shahabadi","year":"2012","journal-title":"Spectrochim. Acta A"},{"key":"ref_65","unstructured":"Mbaba, M. (2019). Repurposing a Polymer Precursor Scaffold for Medicinal Application: Synthesis, Characterization and Biological Evaluation of Ferrocenyl 1,3-Benzoxazine Derivatives as Potential Antiprotozoal and Anticancer Agents. [Ph.D. Thesis, Rhodes University]."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s10812-013-9811-7","article-title":"Mechanisms for binding between methylene blue and DNA","volume":"80","author":"Vardevanyan","year":"2013","journal-title":"J. Appl. Spectrosc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/cyto.990060304","article-title":"Fluorescence studies of Hoechst 33342 with supercoiled and relaxed plasmid pBR322 DNA","volume":"6","author":"Sandhu","year":"1985","journal-title":"Cytometry A"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bucevi\u010dius, J., Lukinavi\u010dius, G., and Gerasimait\u0117, R. (2018). The use of hoechst dyes for DNA staining and beyond. Chemosensors, 6.","DOI":"10.3390\/chemosensors6020018"},{"key":"ref_69","unstructured":"Furniss, B.S., Hannaford, A.J., Smith, P.W.G., and Tatchell, A.R. (1989). Vogel\u2019s Text Book of Practical Organic Chemistry, Longmann Scientific & Technical. [5th ed.]."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4269\/ajtmh.1993.48.205","article-title":"Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia","volume":"48","author":"Makler","year":"1993","journal-title":"Am. J. Trop. Med. Hyg."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/5\/1333\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:31:25Z","timestamp":1760160685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/5\/1333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,2]]},"references-count":70,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["molecules26051333"],"URL":"https:\/\/doi.org\/10.3390\/molecules26051333","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,2]]}}}