ABSTRACT
Zinc(II) (5), indium(III) (6), and lutetium(III) (7) phthalocyanines (Pcs) peripherally substituted with poly (ethylene glycol) (PEG) monomethyl ether 2000 (PEGME-2000) blocks were synthesized via Sonogashira coupling reaction with high yields and their photophysical, photochemical and photobiological properties were investigated. We elucidated the interactions of these compounds with calf thymus DNA and bovine serum albumin (BSA), and determined K(DNA) and K(BSA) binding constants at degrees of 105 and 106, respectively. Singlet oxygen quantum yields were found (Ф∆ = 0.44, 0.54, and 0.68 for 5, 6, and 7, respectively). Thermodynamic parameters, as well as thermal denaturation profile of double-stranded CT-DNA were examined to determine the type of binding mode. According to our experimental data, we report that PEGME-2000 favors the formation of binary complex between DNA, and phthalocyanine complexes. Therein, thermodynamic data suggest that this binding mode is indeed spontaneous under reported conditions, and rather non-specific. Additionally, Pcs 5, 6, and 7 substituted with PEGME-2000 blocks showed antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi (yeast), and Pc 5 had the highest antimicrobial activity among them, as revealed by disc diffusion assay results. In short, our results suggest that these compounds could be used for photodynamic therapy, they have both antibacterial and antifungal activity, and the binding ability of new phthalocyanines 5, 6, and 7 with BSA paves the way for their utilization as drug vehicle in blood plasma.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Photosensitizing Agents/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Cattle , DNA/chemistry , Ethers/chemistry , Ethers/pharmacology , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Indium/chemistry , Indium/pharmacology , Indoles/chemistry , Indoles/pharmacology , Isoindoles , Lutetium/chemistry , Lutetium/pharmacology , Microbial Sensitivity Tests , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Photochemical Processes , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Serum Albumin, Bovine/chemistry , Zinc CompoundsABSTRACT
In this study, morpholinoethoxy-substituted metal-free (3), zinc(II) (4) and indium(III) (5) phthalocyanines were synthesized. These phthalocyanines were converted to their water-soluble quaternized derivatives (3Q-5Q) using excess methyl iodide as a quaternization agent. All these phthalocyanines (Pcs) were characterized by elemental analysis and different spectroscopic methods such as FT-IR, 1H NMR, UV-Vis and mass spectrometry. The photophysical and photochemical properties such as fluorescence and generation of singlet oxygen were investigated for determination of these phthalocyanines as photosensitizers in photodynamic therapy (PDT) applications. The binding properties of quaternized phthalocyanines (3Q-5Q) to calf thymus DNA (CT-DNA) were investigated by UV-Vis and fluorescence spectrophotometric methods. The quenching effect of all quaternized phthalocyanines on the fluorescence intensity of SYBR Green-DNA complex was determined. The mixtures of 3Q, 4Q or 5Q and DNA solutions were used to determine the change in T m of double helix DNA with thermal denaturation profile. In addition, thermodynamic parameters considering their aggregation in buffer solution, which shows the spontaneity of the reactions between DNA and quaternized Pcs were investigated. On the other hand, in vitro phototoxicity and cytotoxicity behavior of the quaternized water-soluble phthalocyanine photosensitizers (3Q-5Q) were tested against the cervical cancer cell line named HeLa for evaluation of their suitability for treatment of cancer by PDT method. Peripherally tetra-substituted neutral and quaternized metal-free and metallophthalocyanines (MPcs) (Zn, In) bearing morpholinoethoxy groups were prepared. The binding of quaternized compounds (3Q-5Q) to CT-DNA were examined using UV-Vis, fluorescence spectra, thermal denaturation profiles and K SV values. Besides, thermodynamic studies indicated that binding of 3Q-5Q to DNA was spontaneous. On the other hand, in vitro phototoxicity and cytotoxicity behavior of the quaternized water-soluble phthalocyanine photosensitizers (3Q-5Q) were tested against the cervical cancer cell line named HeLa for evaluation of their suitability for treatment of cancer by PDT method.
