Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency
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...
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doaj-f7b90f3c453b4513bf7cd8f86ca3f4182021-03-03T00:02:53ZengMDPI AGMolecules1420-30492021-03-01261333133310.3390/molecules26051333Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal PotencyMziyanda Mbaba0Laura M. K. Dingle1Ayanda I. Zulu2Dustin Laming3Tarryn Swart4Jo-Anne de la Mare5Heinrich C. Hoppe6Adrienne L. Edkins7Setshaba D. Khanye8Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Biochemistry and Microbiology, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDepartment of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaA 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.https://www.mdpi.com/1420-3049/26/5/1333organometallicbioorganometallicferrocenecoumarinoxazinemalaria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mziyanda Mbaba Laura M. K. Dingle Ayanda I. Zulu Dustin Laming Tarryn Swart Jo-Anne de la Mare Heinrich C. Hoppe Adrienne L. Edkins Setshaba D. Khanye |
spellingShingle |
Mziyanda Mbaba Laura M. K. Dingle Ayanda I. Zulu Dustin Laming Tarryn Swart Jo-Anne de la Mare Heinrich C. Hoppe Adrienne L. Edkins Setshaba D. Khanye Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency Molecules organometallic bioorganometallic ferrocene coumarin oxazine malaria |
author_facet |
Mziyanda Mbaba Laura M. K. Dingle Ayanda I. Zulu Dustin Laming Tarryn Swart Jo-Anne de la Mare Heinrich C. Hoppe Adrienne L. Edkins Setshaba D. Khanye |
author_sort |
Mziyanda Mbaba |
title |
Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency |
title_short |
Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency |
title_full |
Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency |
title_fullStr |
Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency |
title_full_unstemmed |
Coumarin-Annulated Ferrocenyl 1,3-Oxazine Derivatives Possessing In Vitro Antimalarial and Antitrypanosomal Potency |
title_sort |
coumarin-annulated ferrocenyl 1,3-oxazine derivatives possessing in vitro antimalarial and antitrypanosomal potency |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2021-03-01 |
description |
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. |
topic |
organometallic bioorganometallic ferrocene coumarin oxazine malaria |
url |
https://www.mdpi.com/1420-3049/26/5/1333 |
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