Design, synthesis and biological evaluation of water soluble and non-aggregated silicon phthalocyanines, naphthalocyanines against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines as potential anticancer agents.

Cancer has become an important public problem in worldwide since cancer incidence and mortality are growing rapidly. In this study, water soluble and non-aggregated silicon (IV) phthalocyanines and naphthalocyanines containing (3,5-bis{3-[3-(diethylamino)phenoxy]propoxy}phenyl)methoxy groups have been synthesized and characterized to investigate their anticancer potential. Their DNA binding/nuclease, topoisomerases inhibition were investigated using UV-Vis absorption, thermal denaturation and agarose gel electrophoresis. The in vitro cytotoxic properties of the compounds on human lung (A549), breast (BT-20), liver (SNU-398), prostate (DU-145), melanoma (SK-Mel 128) carcinoma and human fibroblast (HFC) normal cell lines were evaluated by using MTT assay. In order to determine the mechanism of cancer cell growth suppression, cell cycle analysis was carried out using flow cytometer on A549 cell line. The Kb values of SiPc1a and SiNc2a were 6.85 ± (0.35) × 106 and 1.72 ± (0.16) × 104 M-1 and Tm values of ct-DNA were calculated as 82.02 °C and 78.07 °C, respectively in the presence of both compounds. The ΔTm values of SiPc1a and SiNc2a were calculated as 6.45 and 2.50 °C, respectively. The nuclease effects of SiPc1a and SiNc2a with supercoiled plasmid pBR322 DNA demonstrated that both compounds did not trigger any DNA nuclease effects at the lowest concentrations without irradiation whereas both compounds in the presence of activating agent (H2O2) showed significant plasmid DNA nuclease actions under irradiation (22.5 J/cm2). SiPc1a and SiNc2a inhibited to topoisomerase I on increasing concentrations whilst they had lower inhibition action toward topoisomerase II that of topoisomerase I. The in vitro cytotoxicity studies displayed that SiPc1a had the highest cytotoxic effects among the tested compounds against A549, SNU-398, SK-MEL128, DU-145, BT-20 and HFC cell lines with CC50 values ranged from 0.49 to 2.99 µM. Furthermore, SiPc1a inhibited cell proliferation by cell cycle arrest in G0/G1 phase. All of these results suggested that SiPc1a is a promising candidate as an anticancer agent.

Recent studies of nitrogen containing heterocyclic compounds as novel antiviral agents: A review.

N-heterocycles are important, not only because of their abundance, but above all because of their chemical, biological and technical significance. They play an important role in biological investigation such as anticancer, antiinflammatory, antibacterial, antiviral, anti-tumor, antidiabetic, etc. In this study, we focused on examining synthesized some 5- or 6-ring N-heterocyclic compounds that showed the antiviral activity in last 5 years, and investigation of these compounds structure-activity relationship studies. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

Triazole substituted metal-free, metallo-phthalocyanines and their water soluble derivatives as potential cholinesterases inhibitors: Design, synthesis and in vitro inhibition study.

In this study, 1,2,3-triazole substituted metal-free and metallo phthalocyanines (4, 5, 6) and their water soluble derivatives (4a, 5a, 6a) were designed, synthesized for the first time and tested in vitro on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Most phthalocyanines exhibited good inhibitory activities on these enzymes. Among the six phthalocyanines and starting compounds, 4a showed the most interesting profile as a submicromolar selective inhibitor of AChE (IC50 = 0.040 µM) and 5a showed the most effective inhibitor of BChE (IC50 = 0.1198 µM).

Design, Synthesis, Characterization and Electrochemical Properties of BODIPY Dyes Containing Mono, Bis-2-Naphthyloxyhexyloxy and 4-(Benzyloxy)Phenoxyhexyloxy Groups.

In this study, the synthesis of boron dipyrromethene dyes containing mono, bis-2-naphthyloxyhexyloxy and 4-(benzyloxy)phenoxyhexyloxy groups has been reported. Boron dipyrromethene dyes were synthesized from the mono, bis-benzaldehyde derivatives with 2,4-dimethylpyrrole in dichloromethane in the presence of trifluoroacetic, 2,3-dichloro-5,6-dicyano-p-benzoquinon, triethyl amine and boron trifluoride diethyl etherate, respectively. Electrochemical characterization of boron dipyrromethene dyes were carried out with voltammetric measurements. Electrochemical studies show that boron dipyrromethene dyes containing mono, bis-2-naphthyloxyhexyloxy and 4-(benzyloxy)phenoxyhexyloxy groups have reversible one reduction potentials unlike irreversible one oxidation potentials. Graphical Abstract ᅟ.

Synthesis and in vitro α-glucosidase and cholinesterases inhibitory actions of water-soluble metallophthalocyanines bearing ({6-[3-(diethylamino)phenoxy]hexyl}oxy groups.

In this paper, we have prepared peripherally tetra-({6-[3-(diethylamino)phenoxy]hexyl}oxy substituted cobalt(II), copper(II), manganese(III) phthalocyanines (3, 4, 5) and their water-soluble derivatives (3a, 4a, 5a). Then, in vitro α-glucosidase and cholinesterases inhibitory actions of the water-soluble 3a, 4a, 5a were examined using spectrophotometric methods. 4a had the highest inhibitory effects among the tested compounds against α-glucosidase due to IC50 values. 4a and 5a had 40 fold higher inhibitory effects than the positive control. For cholinesterases, the compounds showed significant inhibitory actions that of galantamine which was used as a positive control. According to the SI value, 3a inhibited acetylcholinesterase enzyme selectively. In kinetic studies, 4a was a mixed inhibitor for α-glucosidase, 3a was a competitive inhibitor for AChE, and 4a was a mixed inhibitor for BuChE. The therapeutic potential of these compounds has been demonstrated by in vitro studies, but these data should be supported by further studies.

Synthesis of nonperipherally tetra-[5-(diethylamino)-2-formylphenoxy] substituted metallophthalocyanines and their electrochemistry.

3-[5-(diethylamino)-2-formylphenoxy]phthalonitrile ( n-TY-CN ), metallophthalocyanines n-TY-Co , n-TY-Cu , and n-TY-Mn bearing [5-(diethylamino)-2-formylphenoxy] groups at nonperipheral positions were prepared for the first time. These compounds were characterized with IR, NMR (only for n-TY-CN ), mass and UV-vis (except n-TY-CN ) spectroscopy. Voltammetric characterizations of n-TY-Co , n-TY-Cu , and n-TY-Mn revealed that while n-TY-Co , n-TY-Cu , and n-TY-Mn showed characteristic Pc ring and/or metal-based reduction reaction, n-TY-Co , n-TY-Cu , and n-TY-Mn were coated on the working electrode during the oxidation processes owing to the cationic electropolymerizations of the [5-(diethylamino)-2-formylphenoxy] substituents.

Novel water soluble BODIPY compounds: Synthesis, photochemical, DNA interaction, topoisomerases inhibition and photodynamic activity properties.

In this study, BODIPY compounds (2, 3, 5 and 6) bearing 3,4-bis(3-pyridin-3-ylpropoxy)benzyl, 4-(3-pyridin-3-ylpropoxy)benzyl groups were synthesized for the first time and further functionalized in a Knoevenagel condensation reaction with 3,4-bis(3-pyridin-3-ylpropoxy)benzaldehyde and 4-(3-pyridin-3-ylpropoxy)benzaldehyde. The water soluble derivatives of BODIPY compounds (3a and 6a) were synthesized by treating BODIPY compounds 3 and 6 with excess iodomethane in DMF. The photochemical properties and DNA binding modes of 3a and 6a were determined using ct-DNA by UV-Vis spectrophotometer and viscometer. DNA cleavage and topoisomerases inhibition properties were studied DNA using agarose gel electrophoresis. Their topoisomerase inhibition mechanisms were investigated at molecular level and correlations with the in vitro results were searched for using molecular docking method. In addition, cytotoxicity and phototoxicity of both compounds were performed on colorectal cancer cells (HCT-116) using MTT assay for 24 h. Annexin V-FITC/PI test was performed to determine the cell death mechanism of 6a induced by irradiation. Finally, 6a-loaded liposomes (LP6a) and PLGA nanoparticles (NP6a) were prepared and their cytotoxic and phototoxic effects were evaluated by MTT assay. The results claimed that 6a had great potential as photosensitizer agent for colorectal cancer owing to its photochemical, DNA interaction and phototoxic properties.