Design and in silico study of the novel coumarin derivatives against SARS-CoV-2 main enzymes

The novel coronavirus (SARS-CoV-2) causes severe acute respiratory syndrome and can be fatal. In particular, antiviral drugs that are currently available to treat infection in the respiratory tract have been experienced, but there is a need for new antiviral drugs that are targeted and inhibit coronavirus. The antiviral properties of organic compounds found in nature, especially coumarins, are known and widely studied. Coumarins, which are also metabolites in many medicinal drugs, should be investigated as inhibitors against coronavirus due to their pharmacophore properties (low toxicity and high pharmacokinetic properties). The easy addition of substituents to the chemical structures of coumarins makes these structures unique for the drug design. This study focuses on factors that increase the molecular binding and antiviral properties of coumarins. Molecular docking studies have been carried out to five different proteins (Spike S1-subunit, NSP5, NSP12, NSP15, and NSP16) of the SARS-CoV-2 and two proteins (ACE2 and VKORC1) of human. The best binding scores for 17 coumarins were determined for NSP12 (NonStructural Protein-12). The highest score (–10.01 kcal/mol) in the coumarin group is 2-morpholinoethan-1-amine substituted coumarin. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analyses of selected ligand-protein complexes were performed. The binding energies in each 5 ns were calculated and it was found that the interaction between ligand and target protein were stable. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group

Polar gruplar içeren ftalosiyanin bileşiklerinin sentezi, karakterizasyonu, fotofiziksel ve fotokimyasal özelliklerinin incelenmesi

POLAR GRUPLAR İÇEREN FTALOSİYANİN BİLEŞİKLERİNİN SENTEZİ, KARAKTERİZASYONU, FOTOFİZİKSEL VE FOTOKİMYASAL ÖZELLİKLERİNİN İNCELENMESİ Ftalosiyanin molekülü ve onun türevleri son yüzyılın ilk zamanlarındaki keşfinden beri önemli boya ve pigment sınıfı moleküllerdir. 18 π elektron sistemine sahiptirler ve aromatik özellik gösterirler. Ftalosiyaninlerin ve metalliftalosiyaninlerin en büyük dezavantajı, su veya organik solventlerdeki zayıf çözünürlükleridir. Ftalosiyanindeki benzen yapısına periferal ve/veya nonperiferaline uygun fonksiyonel gruplar yerleştirilerek protik ve protik olmayan çözücülerde çözünürlüğünün arttırılabileceği bulunmuştur. Metalliftalosiyanin komplekslerinin görünür ışığın kırmızı bölgesinde yoğun absorpsiyona sahip olmaları bu bileşiklerin kanserin fotodinamik tedavisi için son derece umut verici fotoduyarlaştırıcılar olduklarını göstermektedir. Ftalosiyaninler, yüksek triplet hal kuantum verimleri, uzun süre triplet ömürleri ve etkili singlet oksijen üretebilme kapasitelerinden dolayı uygun fotoduyarlaştırıcı adaylarıdır. Kumarinler, bir benzen ve piron halkasından oluşan heterohalkalı bileşiklerdir ve biyolojik aktivitelerinden dolayı önemli organik bileşiklerdir. Bu çalışmada 7-hidroksi-3-(p-tiyometilfenil)kumarin bileşiği yüksek floresans özelliği ve fotodinamik terapi de takip edilebilme özelliği gösterebileceğinden dolayı seçilmiştir. Bu çalışmada, fenol, iyot ve kumarin grubu taşıyan yeni ftalosiyaninler sentezlendi ve karakterize edildi. Ayrıca, bu bileşiklerin fotoduyarlaştırıcı olarak kanserin fotodinamik tedavisinde aktivitesini anlamak için fotofizikokimyasal özellikleri araştırılmıştır. SUMMARY SYNTHESIS, CHARACTERIZATION AND INVESTIGATION OF PHOTOPHYSICAL AND PHOTOCHEMICAL PROPERTIES OF PHTHALOCYANINE COMPOUNDS INCLUDING POLAR GROUPS Phthalocyanine molecule and its derivatives have been an important class of dyes and pigments since their first synthesis early in the last century. They have 18 π electron systems and they are a class of aromatic compounds. A major disadvantage of phhthalocyanines and metallophthalocyanines is their low solubility in organic solvents or in water. It has been found that suitable functional groups on the peripheral and/or non-peripheral benzene rings of the phthalocyanine structure can improve the solubility in protic or nonprotic solvents. Metallophthalocyanine complexes have been proved as highly promising photosensitizers for photodynamic therapy due to their intense absorption in the red region of the visible light. They are appropriate candidates as photosensitizers due to their high triplet state quantum yields, long triplet lifetimes and effectively singlet oxygen generation capability. Coumarins are heterocyclic molecules which consist of a benzene and a pyrone ring and very important organic compounds because of their biological activity. In this study, 7-hydroxy-3-(4-thiomethylphenyl)coumarin have been chosen due to their high fluorescence and imaging properties to photodynamic therapy Additionally, we also synthesized and characterized new phthalocyanines bearing phenol, iodine and coumarine groups,we investigated their photophysicochemical properties for the determination of photodynamic theraphy activity as photosensitizers

Polar gruplar içeren ftalosiyanin bileşiklerinin sentezi, karakterizasyonu, fotofiziksel ve fotokimyasal özelliklerinin incelenmesi

ÖZET POLAR GRUPLAR İÇEREN FTALOSİYANİN BİLEŞİKLERİNİN SENTEZİ, KARAKTERİZASYONU, FOTOFİZİKSEL VE FOTOKİMYASAL ÖZELLİKLERİNİN İNCELENMESİFtalosiyanin molekülü ve onun türevleri son yüzyılın ilk zamanlarındaki keşfinden beri önemli boya ve pigment sınıfı moleküllerdir. 18 π elektron sistemine sahiptirler ve aromatik özellik gösterirler. Ftalosiyaninlerin ve metalliftalosiyaninlerin en büyük dezavantajı, su veya organik solventlerdeki zayıf çözünürlükleridir. Ftalosiyanindeki benzen yapısına periferal ve/veya nonperiferaline uygun fonksiyonel gruplar yerleştirilerek protik ve protik olmayan çözücülerde çözünürlüğünün arttırılabileceği bulunmuştur.Metalliftalosiyanin komplekslerinin görünür ışığın kırmızı bölgesinde yoğun absorpsiyona sahip olmaları bu bileşiklerin kanserin fotodinamik tedavisi için son derece umut verici fotoduyarlaştırıcılar olduklarını göstermektedir. Ftalosiyaninler, yüksek triplet hal kuantum verimleri, uzun süre triplet ömürleri ve etkili singlet oksijen üretebilme kapasitelerinden dolayı uygun fotoduyarlaştırıcı adaylarıdır. Kumarinler, bir benzen ve piron halkasından oluşan heterohalkalı bileşiklerdir ve biyolojik aktivitelerinden dolayı önemli organik bileşiklerdir. Bu çalışmada 7-hidroksi-3-(p-tiyometilfenil)kumarin bileşiği yüksek floresans özelliği ve fotodinamik terapi de takip edilebilme özelliği gösterebileceğinden dolayı seçilmiştir.Bu çalışmada, fenol, iyot ve kumarin grubu taşıyan yeni ftalosiyaninler sentezlendi ve karakterize edildi. Ayrıca, bu bileşiklerin fotoduyarlaştırıcı olarak kanserin fotodinamik tedavisinde aktivitesini anlamak için fotofizikokimyasal özellikleri araştırılmıştır.SUMMARYSYNTHESIS, CHARACTERIZATION AND INVESTIGATION OF PHOTOPHYSICAL AND PHOTOCHEMICAL PROPERTIES OF PHTHALOCYANINE COMPOUNDS INCLUDING POLAR GROUPSPhthalocyanine molecule and its derivatives have been an important class of dyes and pigments since their first synthesis early in the last century. They have 18 π electron systems and they are a class of aromatic compounds. A major disadvantage of phhthalocyanines and metallophthalocyanines is their low solubility in organic solvents or in water. It has been found that suitable functional groups on the peripheral and/or non-peripheral benzene rings of the phthalocyanine structure can improve the solubility in protic or nonprotic solvents. Metallophthalocyanine complexes have been proved as highly promising photosensitizers for photodynamic therapy due to their intense absorption in the red region of the visible light. They are appropriate candidates as photosensitizers due to their high triplet state quantum yields, long triplet lifetimes and effectively singlet oxygen generation capability. Coumarins are heterocyclic molecules which consist of a benzene and a pyrone ring and very important organic compounds because of their biological activity. In this study, 7-hydroxy-3-(4-thiomethylphenyl)coumarin have been chosen due to their high fluorescence and imaging properties to photodynamic therapyAdditionally, we also synthesized and characterized new phthalocyanines bearing phenol, iodine and coumarine groups,we investigated their photophysicochemical properties for the determination of photodynamic theraphy activity as photosensitizers

In silico, 6lu7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2

The new emerging coronavirus (SARS-CoV-2) has become a global health problem with very rapid transmission from person to person, causing severe acute respiratory problems. In the circumstance, the discovery of vaccines or drugs to eradicate or reduce the impact of the COVID-19 has made it imperative to develop new approaches. In the current situation, many drugs on the drug bank have been researched computationally, and there has not been an emphasis on synthetic effort. We tested 42 coumarin derivatives (1a-14c) containing 14 different substituents, which are secondary metabolites of plants, and the anticoagulant Coumadin (warfarin) drug as a reference by Molecular Docking calculation technique on 6LU7 main protease of the coronavirus. Optimized geometries, electron motions and energy values of all coumarins were also determined using the Density Functional Theory (DFT) method. The drug properties of coumarins were estimated using the ADME-Tox test method. Coumarins formed strong interactions with HIS41, CYS145, and other amino acids in the active site of the main protease. In general, 6,7-dihydroxy-3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, biphenyl (for 10a,-8.6 kcal/mol; 10b,-8.3 kcal/mol; 10c,-7.9 kcal/mol) and 4-trifluoromethylphenyl (for 13a,-8.1 kcal/mol; 13b,-8.1 kcal/mol; 13c-8.3 kcal/mol) substituted coumarin had the highest score. The coumarins data reported in this study serves as a stepping stone for in vitro and in vivo experimental research for vaccine development purposes. © 2020, Turkish Chemical Society. All rights reserved

In silico, 6LU7 protein inhibition using dihydroxy-3-phenyl coumarin derivatives for SARS-CoV-2

The new emerging coronavirus (SARS-CoV-2) has become a global health problem with very rapid transmission from person to person, causing severe acute respiratory problems. In the circumstance, the discovery of vaccines or drugs to eradicate or reduce the impact of the COVID-19 has made it imperative to develop new approaches. In the current situation, many drugs on the drug bank have been researched computationally, and there has not been an emphasis on synthetic effort. We tested 42 coumarin derivatives (1a-14c) containing 14 different substituents, which are secondary metabolites of plants, and the anticoagulant Coumadin (warfarin) drug as a reference by Molecular Docking calculation technique on 6LU7 main protease of the coronavirus. Optimized geometries, electron motions and energy values of all coumarins were also determined using the Density Functional Theory (DFT) method. The drug properties of coumarins were estimated using the ADME-Tox test method. Coumarins formed strong interactions with HIS41, CYS145, and other amino acids in the active site of the main protease. In general, 6,7-dihydroxy-3-phenylcoumarin derivatives gave relatively higher scores, and for all coumarins, biphenyl (for 10a,-8.6 kcal/mol; 10b,-8.3 kcal/mol; 10c,-7.9 kcal/mol) and 4-trifluoromethylphenyl (for 13a,-8.1 kcal/mol; 13b,-8.1 kcal/mol; 13c-8.3 kcal/mol) substituted coumarin had the highest score. The coumarins data reported in this study serves as a stepping stone for in vitro and in vivo experimental research for vaccine development purposes. © 2020, Turkish Chemical Society. All rights reserved

Novel Hexadeca-Substituted Metal Free and Zinc(II) Phthalocyanines; Design, Synthesis and Photophysicochemical Properties

The syntheses of a novel 1,4,8,11,15,18,22,25-octahexyloxy-2,3,9,10,16,17,23,24-octa-(4-trifluoromethoxyphenyl) phthalocyanine (3a) and its zinc(II) phthalocyanine derivative (3b) have been described and characterized by elemental analysis,1H NMR, 13C NMR, 19F NMR, mass, UV-Vis and FT-IR. The newly prepared metal-free phthalocyanine and its zinc(II) counterpart are soluble in most organic solvents. The photophysical and photochemical properties such as aggregation, fluorescence, singlet oxygen generation and photodegradation under light irradiation of these phthalocyanines have been investigated in DMF. The hexadeca-substituted phthalocyanines (3a and 3b) showed longer absorption and emission wavelength values when compared to that of reported phthalocyanine derivatives due to substitution of the all possible positions in the phthalocyanine framework. The zinc(II) phthalocyanine derivative does not only have a good singlet oxygen generation but also has other photophysicochemical properties that enables this phthalocyanine to be useful as a photosensitizer for cancer treatment using photodynamic therapy