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.
Keywords: Antiprotozoal, anticancer, drugs, phenothiazine, scaffold, biological activities.
Current Medicinal Chemistry
Title:Recent Advances in the Medicinal Chemistry of Phenothiazines, New Anticancer and Antiprotozoal Agents
Volume: 28 Issue: 38
Author(s): Alonzo González-González, Lenci K. Vazquez-Jimenez, Alma D. Paz-González, María Laura Bolognesi and Gildardo Rivera*
Affiliation:
- Laboratorio de Biotecnologia Farmaceutica, Centro de Biotecnología Genomica, Instituto Politecnico Nacional, 88710 Reynosa,Mexico
Keywords: Antiprotozoal, anticancer, drugs, phenothiazine, scaffold, biological activities.
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.
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Cite this article as:
González-González Alonzo, Vazquez-Jimenez K. Lenci , Paz-González D. Alma , Bolognesi Laura María and Rivera Gildardo *, Recent Advances in the Medicinal Chemistry of Phenothiazines, New Anticancer and Antiprotozoal Agents, Current Medicinal Chemistry 2021; 28 (38) . https://dx.doi.org/10.2174/0929867328666210405120330
DOI https://dx.doi.org/10.2174/0929867328666210405120330 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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