Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency
| dc.contributor.author | Mbaba, Mziyanda | |
| dc.contributor.author | Dingle, Laura M K | |
| dc.contributor.author | Zulu, Ayanda I | |
| dc.contributor.author | Laming, Dustin | |
| dc.contributor.author | Swart, Tarryn | |
| dc.contributor.author | de la Mare, Jo-Anne | |
| dc.contributor.author | Hoppe, Heinrich C | |
| dc.contributor.author | Edkins, Adrienne L | |
| dc.contributor.author | Khanye, Setshaba D | |
| dc.date.accessioned | 2021-10-26T10:14:29Z | |
| dc.date.available | 2021-10-26T10:14:29Z | |
| dc.date.issued | 2021-03-02 | |
| dc.date.updated | 2021-03-12T14:38:26Z | |
| dc.description.abstract | 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 <i>P. falciparum</i>) over the investigated trypanosomiasis causal agent (<i>T. b. brucei</i> 427) with mostly single digit micromolar IC<sub>50</sub> 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 α-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 (<b>11b</b>) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects. | en_US |
| dc.identifier | 10.3390/molecules26051333 | |
| dc.identifier.apacitation | Mbaba, M., Dingle, L. M. K., Zulu, A. I., Laming, D., Swart, T., de la Mare, J., ... Khanye, S. D. (2021). Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency. <i>Molecules</i>, 26(5), 1333. http://hdl.handle.net/11427/35293 | en_ZA |
| dc.identifier.chicagocitation | Mbaba, Mziyanda, Laura M K Dingle, Ayanda I Zulu, Dustin Laming, Tarryn Swart, Jo-Anne de la Mare, Heinrich C Hoppe, Adrienne L Edkins, and Setshaba D Khanye "Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency." <i>Molecules</i> 26, 5. (2021): 1333. http://hdl.handle.net/11427/35293 | en_ZA |
| dc.identifier.citation | Mbaba, M., Dingle, L.M.K., Zulu, A.I., Laming, D., Swart, T., de la Mare, J., Hoppe, H.C. & Edkins, A.L. et al. 2021. Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency. <i>Molecules.</i> 26(5):1333. http://hdl.handle.net/11427/35293 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Mbaba, Mziyanda AU - Dingle, Laura M K AU - Zulu, Ayanda I AU - Laming, Dustin AU - Swart, Tarryn AU - de la Mare, Jo-Anne AU - Hoppe, Heinrich C AU - Edkins, Adrienne L AU - Khanye, Setshaba D AB - 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 <i>P. falciparum</i>) over the investigated trypanosomiasis causal agent (<i>T. b. brucei</i> 427) with mostly single digit micromolar IC<sub>50</sub> 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 α-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 (<b>11b</b>) support hemozoin inhibition and DNA interaction as likely mechanistic modalities by which this class of compounds may act to produce plasmocidal and antitrypanosomal effects. DA - 2021-03-02 DB - OpenUCT DP - University of Cape Town IS - 5 J1 - Molecules LK - https://open.uct.ac.za PY - 2021 T1 - Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency TI - Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency UR - http://hdl.handle.net/11427/35293 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/35293 | |
| dc.identifier.vancouvercitation | Mbaba M, Dingle LMK, Zulu AI, Laming D, Swart T, de la Mare J, et al. Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency. Molecules. 2021;26(5):1333. http://hdl.handle.net/11427/35293. | en_ZA |
| dc.publisher.department | Department of Chemistry | en_US |
| dc.publisher.faculty | Faculty of Science | en_US |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
| dc.source | Molecules | en_US |
| dc.source.journalissue | 5 | en_US |
| dc.source.journalvolume | 26 | en_US |
| dc.source.pagination | 1333 | en_US |
| dc.source.uri | https://www.mdpi.com/journal/molecules | |
| dc.title | Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency | en_US |
| dc.type | Journal Article | en_US |