Phthalocyanine complexes with (4-isopropylbenzyl)oxy substituents: preparation and evaluation of anti-carbonic anhydrase, anticholinesterase enzymes and molecular docking studies

Abstract In this study, the preparation, aggregation behavior and investigation of carbonic anhydrase and cholinesterase enzyme inhibition features of non-peripherally (4-isopropylbenzyl)oxy-substituted phthalocyanines (4–6) are reported for the first time. The chemical structures of these new phthalocyanines were elucidated by UV-Vis (ultraviolet-visible), FT-IR (Fourier transform infrared spectrometry), NMR (nuclear magnetic resonance) and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry. The substitution of 4-isopropylbenzyl)oxy groups benefits a remarkable solubility and redshift of the phthalocyanines Q-band. Also, these complexes were tested against some enzymes such as butyrylcholinesterase enzyme, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme. The phthalocyanine complexes showed Ki values of in the range of 478.13 ± 57.25–887.25 ± 101.20 µM against hCA I, 525.16 ± 45.87–921.14 ± 81.25 µM against hCA II, 68.33 ± 9.13–201.15 ± 35.86 µM against AChE and 86.25 ± 13.65–237.54 ± 24.7 µM against BChE. Molecular docking studies were performed to investigate the binding modes and interaction energies of the (2–6) complexes with the hCA I (PDB ID:1BMZ), hCA II (PDB ID:2ABE), AChE (PDB ID:4EY6) and BChE (PDB ID:2PM8). Graphical Abstract Communicated by Ramaswamy H. Sarma

[1]  I. Gülçin,et al.  Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer's agents. , 2019, Bioorganic chemistry.

[2]  I. Gulcin,et al.  Novel tribenzylaminobenzolsulphonylimine based on their pyrazine and pyridazines: Synthesis, characterization, antidiabetic, anticancer, anticholinergic, and molecular docking studies. , 2019, Bioorganic chemistry.

[3]  M. Wierzchowski,et al.  Nanomolar photodynamic activity of porphyrins bearing 1,4,7-trioxanonyl and 2-methyl-5-nitroimidazole moieties against cancer cells. , 2019, Journal of photochemistry and photobiology. B, Biology.

[4]  I. Gulcin,et al.  Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials. , 2019, Bioorganic chemistry.

[5]  Burak Yildiz,et al.  Unsymmetrically pyrazole-3-carboxylic acid substituted phthalocyanine-based photoanodes for use in water splitting photoelectrochemical and dye-sensitized solar cells , 2019, Solar Energy.

[6]  I. Gulcin,et al.  Synthesis and biological evaluation of bromophenol derivatives with cyclopropyl moiety: Ring opening of cyclopropane with monoester. , 2019, Bioorganic chemistry.

[7]  I. Gulcin,et al.  Novel 2-aminopyridine liganded Pd(II) N-heterocyclic carbene complexes: Synthesis, characterization, crystal structure and bioactivity properties. , 2019, Bioorganic chemistry.

[8]  M. Nebioğlu,et al.  Phthalocyanines with bromobenzenesulfanyl substituents at non-peripheral position: Preparation, photophysical and photochemical properties , 2019, Porphyrin Science by Women.

[9]  I. Gulcin,et al.  Novel eugenol bearing oxypropanolamines: Synthesis, characterization, antibacterial, antidiabetic, and anticholinergic potentials. , 2019, Bioorganic chemistry.

[10]  I. Gulcin,et al.  Synthesis, characterization, molecular docking and biological activities of novel pyrazoline derivatives , 2019, Archiv der Pharmazie.

[11]  I. Gulcin,et al.  Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors. , 2019, Bioorganic chemistry.

[12]  Elenilze F B Ferreira,et al.  Hierarchical Virtual Screening of Potential Insectides Inhibitors of Acetylcholinesterase and Juvenile Hormone from Temephos , 2019, Pharmaceuticals.

[13]  Emre Güzel.  Dual-purpose zinc and silicon complexes of 1,2,3-triazole group substituted phthalocyanine photosensitizers: synthesis and evaluation of photophysical, singlet oxygen generation, electrochemical and photovoltaic properties , 2019, RSC advances.

[14]  T. Goslinski,et al.  Photodynamic inactivation of Enterococcus faecalis by conjugates of zinc(II) phthalocyanines with thymol and carvacrol loaded into lipid vesicles , 2019, Inorganica Chimica Acta.

[15]  E. Bursal,et al.  Phytochemical content, antioxidant activity, and enzyme inhibition effect of Salvia eriophora Boiss. & Kotschy against acetylcholinesterase, α-amylase, butyrylcholinesterase, and α-glycosidase enzymes. , 2019, Journal of food biochemistry.

[16]  P. Taslimi,et al.  Synthesis, characterization, crystal structure of the coordination polymer Zn(II) with thiosemicarbazone of glyoxalic acid and their inhibitory properties against some metabolic enzymes. , 2019, Bioorganic chemistry.

[17]  M. Nebioğlu,et al.  High Photosensitized Singlet Oxygen Generating Zinc and Chloroindium Phthalocyanines Bearing (4‐isopropylbenzyl)oxy Groups as Potential Agents for Photophysicochemical Applications , 2019, ChemistrySelect.

[18]  S. E. Kariper,et al.  Computational study of some fluoroquinolones: Structural, spectral and docking investigations , 2018 .

[19]  V. Ahsen,et al.  Sulfanyl vs sulfonyl, 4,5- vs 3,6- position. How structural variations in phthalonitrile substitution affect their infra-red, crystallographic and Hirshfeld surface analyses , 2018 .

[20]  Ruchi Malik,et al.  Identification of novel acetylcholinesterase inhibitors through e-pharmacophore-based virtual screening and molecular dynamics simulations , 2017, Journal of biomolecular structure & dynamics.

[21]  A. Erdoğmuş,et al.  Synthesis and photophysicochemical properties of novel thiadiazole-substituted zinc (II), gallium (III) and silicon (IV) phthalocyanines for photodynamic therapy , 2017 .

[22]  T. Torres,et al.  Octacationic and axially di-substituted silicon (IV) phthalocyanines for photodynamic inactivation of bacteria , 2017 .

[23]  H. Kantekin,et al.  Tetra(3-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenoxy) substituted cobalt, iron and manganese phthalocyanines: Synthesis and electrochemical analysis , 2017 .

[24]  A. Erdoğmuş,et al.  Novel sulfonated hydrophilic indium(III) and gallium(III) phthalocyanine photosensitizers: preparation and investigation of photophysicochemical properties , 2017 .

[25]  M. Kimura,et al.  Discotic liquid crystals of transition metal complexes, 53†: synthesis and mesomorphism of phthalocyanines substituted by m-alkoxyphenylthio groups , 2017 .

[26]  B. Bilgin-Eran,et al.  Lyotropic liquid crystalline phthalocyanines containing 4-((S)-3,7-dimethyloctyloxy)phenoxy moieties , 2016 .

[27]  A. Tabak,et al.  New metal complexes with diclofenac containing 2-pyridineethanol or 2-pyridinepropanol: synthesis, structural, spectroscopic, thermal properties, catechol oxidase and carbonic anhydrase activities , 2016 .

[28]  P. Tandon,et al.  Computational approaches to find the active binding sites of biological targets against busulfan , 2016, Journal of Molecular Modeling.

[29]  C. Supuran,et al.  Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: an in vitro study , 2016, Journal of enzyme inhibition and medicinal chemistry.

[30]  B. Salih,et al.  Synthesis, characterization, electrochemistry and VOC sensing properties of novel ball-type dinuclear metallophthalocyanines , 2014 .

[31]  A. Gül,et al.  Synthesis and photophysical properties of novel hexadeca-substituted phthalocyanines bearing three different groups , 2014 .

[32]  Armağan Atsay,et al.  Synthesis, characterization and photodynamic activity of a new amphiphilic zinc phthalocyanine , 2013 .

[33]  C. Supuran,et al.  In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II. , 2008, Bioorganic & medicinal chemistry.

[34]  V. Ahsen,et al.  Synthesis, photophysical and photochemical properties of poly(oxyethylene)-substituted zinc phthalocyanines. , 2007, Dalton transactions.

[35]  D. Ekinci,et al.  In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases , 2007 .

[36]  C. Supuran,et al.  Carbonic anhydrase activators: the first X-ray crystallographic study of an adduct of isoform I. , 2006, Bioorganic & medicinal chemistry letters.

[37]  T. Nyokong,et al.  Octabutylthiophthalocyaninatoiron(II): electrochemical properties and interaction with cyanide , 2002 .

[38]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[39]  J. Edsall,et al.  Esterase activities of human carbonic anhydrases B and C. , 1967, The Journal of biological chemistry.

[40]  D. Burk,et al.  The Determination of Enzyme Dissociation Constants , 1934 .

[41]  Ö. Çelikbıçak,et al.  Comparative Electrochemistry and Electrochromic Application of Novel Binuclear Double‐Decker Rare Earth Metal Phthalocyanines Bearing 4-(hydroxyethyl)phenoxy Moieties , 2019, Journal of The Electrochemical Society.

[42]  Vladimir O. Popov,et al.  3D structure of the natural tetrameric form of human butyrylcholinesterase as revealed by cryoEM, SAXS and MD. , 2019, Biochimie.

[43]  D. Ekinci,et al.  In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases. , 2007, Journal of enzyme inhibition and medicinal chemistry.

[44]  A. G. Gürek,et al.  Octakis(alkylthio)-substituted phthalocyanines and their interactions with silver(I) and palladium(II) ions , 1994 .

[45]  J. Hirose,et al.  [Carbonic anhydrase]. , 1983, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.