Affiliation:
1. Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnología Genomica, Instituto Politecnico Nacional, 88710 Reynosa, Mexico
2. Department of Pharmacy and Biotechnology, Alma Mater Studiorum- University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy
Abstract
Background:
Molecules with a phenothiazine scaffold have been considered versatile
organic structures with a wide variety of biological activities, such as antipsychotic, anticancer,
antibacterial, antifungal, antiviral, anti-inflammatory, antimalarial, and trypanocidal,
etc. It was first discovered in the 19th century as a histochemical dye, phenothiazine methylene
blue. Since then, its derivatives have been studied, showing new activities; moreover,
they have also been repurposed.
Objective:
This review aims to describe the main synthetic routes of phenothiazines and, particularly,
the anticancer and antiprotozoal activities reported during the second decade of the
2000s (2010 - 2020).
Results:
Several studies on phenothiazines against cancer and protozoa have revealed that
these compounds show IC50 values in the micromolar and near nanomolar range. The structural
analyses have revealed that compounds bearing halogens or electron-withdrawing
groups at 2-position have favorable anticancer activity. Phenothiazine dyes have shown a
photosensitizing activity against trypanosomatids at a micromolar range. Tetra and pentacyclic
azaphenothiazines are structures with a high broad-spectrum anticancer activity.
Conclusion:
The phenothiazine scaffold is favorable for developing anticancer agents, especially
those bearing halogens and electron-withdrawing groups bound at 2-position with enhanced
biological activities through a variety of aromatic, aliphatic and heterocyclic substituents
in the thiazine nitrogen. Further studies are warranted along these investigation lines to
attain more active anticancer and antiprotozoal compounds with minimal to negligible cytotoxicity.
Funder
Secretaria de Investigacion y Posgrado del Instituto Politecnico Nacional
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
8 articles.
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1. In vitro study of antioxidant, antigylycation, sugar hydrolysis enzyme inhibitory effect and molecular in silico docking study of angularly condensed diquinothiazines;Journal of Molecular Structure;2024-01
2. Synthesis, spectral characterizations, vibrational spectroscopy, DFT-computations, antibacterial, antioxidant, and molecular docking studies of the novel (Z)-2-(5-((10-hexyl-10H-phenothiazin-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetic acid;Journal of Molecular Structure;2023-11
3. Synthesis, Characterization and Anticancer Molecular Docking Studies of Phenothiazine Derivatives – A Green Chemical Approach;ChemistrySelect;2023-09-07
4. Anticancer activities of tetra-, penta-, and hexacyclic phenothiazines modified with quinoline moiety.;Journal of Molecular Structure;2023-09
5. Phenothiazines as anti-cancer agents: SAR overview and synthetic strategies;European Journal of Medicinal Chemistry;2023-06