带吡啶丙氧取代基的非边缘八取代锌(II)酞菁类化合物——抗菌、抗癌光动力和声动力活性

Non-peripheral octasubstituted zinc(II) phthalocyanines bearing pyridinepropoxy substituents - Antibacterial, anticancer photodynamic and sonodynamic activity

JOURNAL OF INORGANIC BIOCHEMISTRY

影响因子:3.2

分区:化学2区 / 无机化学与核化学1区生化与分子生物学3区

发表日期:2025 Jan

作者: Marcin Wysocki, Daniel Ziental, Zekeriya Biyiklioglu, Malgorzata Jozkowiak, Hüseyin Baş, Jolanta Dlugaszewska, Hanna Piotrowska-Kempisty, Emre Güzel, Lukasz Sobotta

DOI: 10.1016/j.jinorgbio.2024.112751

摘要

本文合成了具有3-和4-吡啶丙氧取代基的非边缘八取代锌(II)酞菁类新型化合物，通过取代酞膦腈的环化反应制备，并对其进行了表征。随后评估其对细菌和癌细胞的光动力和声动力活性。此外，还评价了其对常见人类酶的抑制活性。在光照条件下测定了1,3-二苯基异苯并呋喃（DPBF，作为单线态氧的非特异性化学猝灭剂）引发的单线态氧生成量，而在超声（1 MHz，3 W）条件下，评估了DPBF在感光剂存在下的稳定性。这两种酞菁在DMSO中表现出较高的光稳定性，在DMF中表现出中等的稳定性，而在DMF中的声稳定性也为中等。计算得出的光诱导单线态氧生成量子产率在DMF中约为0.33，在DMSO中约为0.67，两者相似。声动力方式下，在1 MHz频率下观察到DPBF的中度分解。两种化合物在光动力和声动力方式中均表现出显著的细菌减少，对MRSA和金黄色葡萄球菌的细菌负载均超过3 log的降低。两种化合物对下咽部肿瘤（FaDu）表现出约50%的存活率降低，在鳞状细胞癌（SCC-25）中观察到高达60%的存活率降低。总之，这种高效酞菁基敏化剂的分子设计具有光动力和声动力应用的潜在治疗价值。

Abstract

The novel non-peripheral octa-substituted zinc(II) phthalocyanines with 3- and 4-pyridinepropoxy substituents were synthesized via cyclization of substituted phthalonitriles and further characterized. Their photodynamic and sonodynamic activity were then assessed toward bacteria and cancer cells. Additionally, inhibition activity against common human enzymes was evaluated. The singlet oxygen generation (with 1,3-diphenylisobenzofuran - DPBF as an unspecific chemical quencher of singlet oxygen) were measured under light irradiation, whereas under ultrasounds (1 MHz, 3 W) the stability of DPBF in the presence of sensitizer was evaluated. Both phthalocyanines revealed high photostability in DMSO and moderate in DMF, whereas the sonostability in DMF was moderate. Calculated light-induced singlet oxygen generation quantum yields were similar for both compounds and oscillated around 0.33 in DMF and 0.67 in DMSO. Sonodynamic manner revealed moderately high DPBF decomposition upon 1 MHz. Significant bacterial reduction was noted in both photodynamic and sonodynamic manner, reaching >3 log reduction against MRSA and S. epidermidis. Both compounds showed ca. 50 % viability reduction toward hypopharyngeal tumor (FaDu). Moreover, up to 60 % viability reduction was observed in squamous cell carcinoma (SCC-25). In summary, this molecular building of the efficient phthalocyanine-based sensitizer is a potential therapeutic for photodynamic and sonodynamic applications.