In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine.

Azulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.

In vitro photodynamic activity of lipid vesicles with zinc phthalocyanine derivative against Enterococcus faecalis.

Zinc(II) phthalocyanine bearing eight non-peripheral 2-propoxy substituents was subjected to physicochemical study and, after incorporation in lipid vesicles, assessed as a potential photosensitizer for antibacterial photodynamic therapy. The phthalocyanine derivative obtained in the macrocyclization reaction was characterized by MS and NMR techniques. Moreover, its chemical purity was confirmed by HPLC analysis. X-ray structural analysis revealed that overcrowding of the phthalocyanine derivative leads to a strong out-of-plane distortion of the π-system of the macrocycle core. In the UV-Vis absorption spectra of zinc(II) phthalocyanine two characteristic bands were found: the Soret (300-450 nm) and the Q band (600-800 nm). Photophysical properties of mono- and diprotonated forms of phthalocyanine derivative were studied with time-resolved fluorescence spectroscopy. Its tri- and tetraprotonated forms could not be obtained, because compound decomposes in higher acid concentrations. The presented zinc(II) phthalocyanine showed values of singlet oxygen generation ΦΔ = 0.18 and 0.16, the quantum yield of the photodecomposition ΦP = 3.06∙10-4 and 1.23∙10-5 and the quantum yield of fluorescence ΦFL = 0.005 and 0.004, designated in DMF and DMSO, respectively. For biological studies, phthalocyanine has been incorporated into modified liposome vesicles containing ethanol. In vitro bacteria photoinactivation study revealed no activity against Escherichia coli and 5.7 log reduction of the Enterococcus faecalis growth.

Dendrimeric Sulfanyl Porphyrazines: Synthesis, Physico-Chemical Characterization, and Biological Activity for Potential Applications in Photodynamic Therapy.

Sulfanyl porphyrazines substituted at their periphery with different dendrimeric moieties up to their first generation were synthesized and characterized by photochemical and biological methods. The presence of a dendrimeric periphery enhanced the spectral properties of the porphyrazines studied. The singlet-oxygen-generation quantum yield of the obtained macrocycles ranged from 0.02 to 0.20 and was strongly dependent on the symmetry of the compounds and the terminal groups of the dendritic outer shell. The in vitro biological effects of three most promising tribenzoporphyrazines were examined; the results indicated their potential as photosensitizers for photodynamic therapy (PDT) against two oral squamous cell carcinoma cell lines derived from the tongue. The highest photocytotoxicity was found for sulfanyl tribenzoporphyrazine that possessed 4-[3,5-di(hydroxymethyl)phenoxy]butyl substituents with nanomolar IC50 values at 10 and 42 nm against CAL 27 and HSC-3 cell lines, respectively.