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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
Conjugates of Tetrapyrrolic Macrocycles as Potential Anticancer Target-Oriented Photosensitizers
Andrew M Korolchuk1,2, Vladimir A Zolottsev3,4, Alexander Y Misharin1
1V.N. Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya Street, 119435, Moscow, Russia.
Abstract:
Photodynamic therapy is a minimally invasive treatment of tumors using photosensitizers, light, and reactive oxygen species, which can destroy cellular structures. With the development of photodynamic therapy, significant efforts have been made to create new efficient photosensitizers with improved delivery to cells, stability, and selectivity against cancer tissues. Naturally occurring tetrapyrrolic macrocycles, such as porphyrins and chlorins, are very attractive as photosensitizers, and their structural modification and conjugation with other biologically active molecules are promising approaches for creating new photosensitizers specifically targeting cancer cells. The present review aims to highlight recent developments in the design, preparation, and investigation of complex conjugates of tetrapyrrolic macrocycles, which can potentially be used as sensitizers for target-oriented photodynamic therapy of cancer. In this review, we discuss the structure, photodynamic effect, and anticancer activity of the following conjugates of tetrapyrrolic macrocycles: (1) conjugates obtained by modifying peripheral substituents in porphyrins and chlorins; (2) conjugates of porphyrins and chlorins with lipids, carbohydrates, steroids, and peptides; (3) conjugates of porphyrins and chlorins with anticancer drugs and some other biologically active molecules; (4) metal-containing conjugates. The question of how the conjugate structure affects its specificity, internalization, localization, and photoinduced toxicity within cancer cells is the focus of this review.
Insights
This review explores novel photosensitizers for photodynamic therapy (PDT) by conjugating tetrapyrrolic macrocycles with various molecules. These advanced conjugates aim to improve cancer targeting and treatment efficacy.
Area of Science:
- Biochemistry
- Organic Chemistry
- Oncology
Background:
- Photodynamic therapy (PDT) utilizes photosensitizers, light, and reactive oxygen species to eliminate cancer cells.
- Developing efficient photosensitizers with enhanced cellular delivery, stability, and cancer selectivity is crucial for advancing PDT.
- Naturally occurring tetrapyrrolic macrocycles (porphyrins, chlorins) are promising photosensitizer scaffolds, with structural modifications offering targeted cancer therapy potential.
Purpose of the Study:
- To review recent advancements in designing and preparing complex conjugates of tetrapyrrolic macrocycles for targeted cancer PDT.
- To analyze the structure, photodynamic effects, and anticancer activity of various tetrapyrrolic macrocycle conjugates.
- To investigate how conjugate structure influences specificity, cellular uptake, localization, and photo-induced toxicity in cancer cells.
Main Methods:
- Review of literature on the design, synthesis, and biological evaluation of tetrapyrrolic macrocycle conjugates.
- Categorization of conjugates based on modification strategies: peripheral substituent modification, conjugation with lipids, carbohydrates, steroids, peptides, anticancer drugs, and metal incorporation.
- Analysis of structure-activity relationships concerning cellular internalization, localization, and photodynamic efficacy.
Main Results:
- Tetrapyrrolic macrocycle conjugates demonstrate potential for targeted PDT.
- Structural modifications and conjugation strategies significantly impact photosensitizer properties, including specificity and efficacy.
- Different conjugate types (e.g., with lipids, peptides, drugs) exhibit varied cellular uptake and localization patterns.
Conclusions:
- Complex conjugates of tetrapyrrolic macrocycles represent a promising strategy for developing targeted photosensitizers in cancer PDT.
- Tailoring conjugate structures is key to optimizing specificity, cellular internalization, and photo-induced toxicity for enhanced anticancer effects.
- Further research into these advanced photosensitizers holds significant potential for improving cancer treatment outcomes.
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