Protoporphyrin IX conjugated to piperazine or morpholine: Photophysical properties and photodynamic activity

IF 4.1 3区工程技术 Q2 CHEMISTRY, APPLIED Dyes and Pigments Pub Date : 2025-01-16 DOI:10.1016/j.dyepig.2025.112649

Maynne Duarte Suriani Franco , Thibault Joseph William Jacques Dit Lapierre , Ana Clara Cassiano Martinho , Naiara Cristina Bessas , Mayara Martins Caetano , Thiago Teixeira Tasso , Marcelo Emílio Beletti , Renata Galvão de Lima , Celso de Oliveira Rezende Júnior , Tayana Mazin Tsubone

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引用次数: 0

Abstract

Designing photosensitizers (PS) with ideal properties for Photodynamic Therapy (PDT) remains challenging, but crucial for advancing PDT as a viable anticancer treatment. Combining porphyrin with potent anticancer agents, such as piperazine and morpholine groups, has the potential to give rise to innovative photosensitizers that exhibit heightened PDT effects in cancer cells. Herein, we present two novel molecules bearing piperazine (PpIX-Pip) or morpholine (PpIX-Morp) groups conjugated to Protoporphyrin IX (PpIX), describing their photophysical and photodynamic characteristics. Analysis of the photophysical properties revealed similar fluorescence quantum yields and lifetimes between PpIX and the conjugated molecules. The PpIX-Pip showed higher production of singlet oxygen and better interaction with HSA in comparison to PpIX-Morp. Cellular uptake assays revealed a greater incorporation rate for PpIX-Pip (37 %) compared to PpIX-Morp (29 %) in HeLa cells. Essentially, both PpIX derivatives exhibited superior uptake efficiencies compared to PpIX alone (17 %). The descending order of IC₅₀ values was PpIX > PpIX-Morp > PpIX-Pip, indicating that the introduction of piperazine and morpholine groups to PpIX elevated the toxicity in HeLa cells. When comparing IC₅₀ values obtained under irradiation to the dark control, it was observed that PpIX-Pip demonstrated higher phototoxic effect (phototherapeutic index, PI > 5), whereas PpIX-Morp exhibits medium phototoxicity towards HeLa cells (PI > 2). Among the newly studied porphyrins, PpIX-Pip displayed a higher singlet oxygen generation rate, and improved cellular uptake as well as lower value of IC₅₀ in the light. This is the first report highlighting the PDT activity of PpIX modified with the N-methylpiperazine group. Our findings open avenues for the design and development of photosensitizers linked to anticancer agent moieties, encompassing groups like piperazine and morpholine.

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来源期刊

Dyes and Pigments 工程技术-材料科学：纺织

CiteScore

8.20

自引率

13.30%

发文量

933

审稿时长

33 days

期刊介绍： Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied. Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media. The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.