摘要
背景:具有吩噻嗪支架的分子被认为是具有多种生物活性的多功能有机结构,如抗精神病药、抗癌药、抗菌药、抗真菌药、抗病毒药、抗炎药、抗疟药和杀锥虫药等。 19世纪作为一种组织化学染料,吩噻嗪亚甲蓝。从那时起,对其衍生物进行了研究,显示出新的活性;此外,它们也被重新利用。 目的:本综述旨在描述吩噻嗪的主要合成路线,特别是 2000 年代第二个十年(2010 - 2020 年)报告的抗癌和抗原虫活性。 结果:几项关于吩噻嗪抗癌和原生动物的研究表明,这些化合物的 IC50 值在微摩尔和接近纳摩尔范围内。结构分析表明,在 2 位带有卤素或吸电子基团的化合物具有良好的抗癌活性。吩噻嗪染料在微摩尔范围内显示出对锥虫的光敏活性。四环和五环氮杂吩噻嗪是具有高广谱抗癌活性的结构。 结论:吩噻嗪支架有利于开发抗癌药物,尤其是那些带有卤素和吸电子基团的抗癌药物,通过噻嗪氮中的多种芳香族、脂肪族和杂环取代基在2-位结合具有增强的生物活性。有必要沿着这些研究路线进行进一步的研究,以获得更具活性的抗癌和抗原生动物化合物,其细胞毒性最小至可忽略不计。
关键词: 抗原虫、抗癌、药物、吩噻嗪、支架、生物活性。
Current Medicinal Chemistry
Title:Recent Advances in the Medicinal Chemistry of Phenothiazines, New Anticancer and Antiprotozoal Agents
Volume: 28 Issue: 38
关键词: 抗原虫、抗癌、药物、吩噻嗪、支架、生物活性。
摘要:
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:
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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