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Review
. 2021 Jun 7;26(11):3453.
doi: 10.3390/molecules26113453.

Pharmacological Activities of Aminophenoxazinones

Jesús G Zorrilla  1 , Carlos Rial  1 , Daniel Cabrera  1 , José M G Molinillo  1 , Rosa M Varela  1 , Francisco A Macías  1
Affiliations
Review

Pharmacological Activities of Aminophenoxazinones

Jesús G Zorrilla et al. Molecules. .

Abstract

Aminophenoxazinones are degradation products resulting from the metabolism of different plant species, which comprise a family of natural products well known for their pharmacological activities. This review provides an overview of the pharmacological properties and applications proved by these compounds and their structural derivatives during 2000-2021. The bibliography was selected according to our purpose from the references obtained in a SciFinder database search for the Phx-3 structure (the base molecule of the aminophenoxazinones). Compounds Phx-1 and Phx-3 are among the most studied, especially as anticancer drugs for the treatment of gastric and colon cancer, glioblastoma and melanoma, among others types of relevant cancers. The main information available in the literature about their mechanisms is also described. Similarly, antibacterial, antifungal, antiviral and antiparasitic activities are presented, including species related directly or indirectly to significant diseases. Therefore, we present diverse compounds based on aminophenoxazinones with high potential as drugs, considering their levels of activity and few adverse effects.

Keywords: Phx-3; aminophenoxazinone; antibacterial; antifungal; cancer; cytotoxicity; drug; in vitro; in vivo; virus.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Prominent benzoxazinones and some of their degradation products.
Scheme 1
Scheme 1
General degradation process of benzoxazinones.
Figure 2
Figure 2
Phenoxazine and aminophenoxazinone structures, and some molecules of their different derivatives, like the drug actinomycin D.
Figure 3
Figure 3
Most studied aminophenoxazinones: 2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazin-3-one (Phx-1), 3-amino-1,4α-dihydro-4α,8-dimethyl-2H-phenoxazin-2-one (Phx-2) and 2-aminophenoxazine-3-one (Phx-3).
Figure 4
Figure 4
Structure of N-(2-hydroxyphenyl)-2-phenazinamine (NHP).
Figure 5
Figure 5
Inhibition of cell growth and induction of apoptosis after treating LN229 cell line with Phx-3. Source: Che et al. [70] by permission from Spandidos Publications Ltd.
Figure 6
Figure 6
Effect of Phx-3 on the body weight of mice transplanted with B16 cells (○: Phx-3 △: positive control ■: negative control). Source: Miyano-Kurosaki et al. [51] by permission from Biol. Pharm. Bull.
Figure 7
Figure 7
Changes in the pHi of MCF-7 cells treated with different concentrations of Phx-3 Source: reproduced from Che et al. [57] with permission from Proc. Japan Acad. Ser. B.
Figure 8
Figure 8
Proapoptotic effects of Phx-3 on (A) MCF-7 and (B) A431 cells. Reproduced from Che et al. [57] with permission of Proc. Japan Acad., Ser. B. * p < 0.01, ** p < 0.001.
Figure 9
Figure 9
Structures of indole, the anticancer drug vincristine and the most active indole derivatives.
Figure 10
Figure 10
Structure of the pyridophenoxazinone derivatives conjugated to L-lysine.
Figure 11
Figure 11
Compound 8 and derivatives obtained by arylation using boronic acids (9–12) or by amination using anilines (13–15).
Figure 12
Figure 12
Phenoxazin derivatives with antibacterial (16) and antimalarial (17 and 18) activity.
Figure 13
Figure 13
Compounds that have exhibited some interesting potential to treat L. major infections.
See this image and copyright information in PMC

References

    1. Butler M.S. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat. Prod. Rep. 2008;25:475–516. doi: 10.1039/b514294f. - DOI - PubMed
    1. Tomoda A., Miyazawa K., Tabuchi T. Prevention of carcinogenesis and development of gastric and colon cancers by 2-Aminophenoxazine-3-one (Phx-3): Direct and indirect Anti-Cancer activity of Phx-3. Int. J. Mol. Sci. 2013;14:17573–17583. doi: 10.3390/ijms140917573. - DOI - PMC - PubMed
    1. Sánchez-Moreiras A.M., Coba de la Peña T., Martínez A., González L., Pellisier F., Reigosa M.J. Mode of action of the hydroxamic acid BOA and other related compounds. Allelopathy. 2004:239–252.
    1. Bravo H.R., Lazo W. Antialgal and antifungal activity of natural hydroxamic acids and related compounds. J. Agric. Food Chem. 1996;44:1569–1571. doi: 10.1021/jf950345e. - DOI - PubMed
    1. Jensen B.M., Adhikari K.B., Schnoor H.J., Juel-Berg N., Fomsgaard I.S., Poulsen L.K. Quantitative analysis of absorption, metabolism, and excretion of benzoxazinoids in humans after the consumption of high- and low-benzoxazinoid diets with similar contents of cereal dietary fibres: A crossover study. Eur. J. Nutr. 2017;56:387–397. doi: 10.1007/s00394-015-1088-6. - DOI - PubMed

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