Synthesis of novel nicotinamide susbstituted phthalocyanine and photodynamic antomicrobial chemotherapy evaluation potentiated by potassium iodide against the gram positive S. aureus and gram negative E. coli.

In the present work, we propose the synthesis of novel nicotinamide subsituted phthlocyanine photosensitizer (PS) and characterized by FTIR, UV-visible, H-NMR and MALDI Toff spectroscopy. Nicotinamide plays a vital rule in the central nervous system and its potential as a therapeutic for neurodegenerative disease. Nicotinamide substituted PS (3) efficiently produced ROS via type-1 process as measured by DCF assay. We observed that our PS after red light illumination (22 J/cm2) killed gram positive S. aureus upto 3 log reduction. Furher the addition of Potassium Iodide (100 mM) significantly potentiated PS at lower concentrations and enhanced the bacterial killing upto 6 log reduction against the S. aureus. We further found that the synergistic effect of PS and KI also eradicated the gram negative E. coli strain at lower concentraion of PS and found to killed E. coli upto 5 log reduction under the red light illumination at 22 J/cm2 of light dose. The conjugation of such biologically important form of vitamin B3 with PS would be a great addition and could pav the way for the novel photodynamic agent in the treatement of cancer and infectious diseases. A new symmetrical Nicotinamide tetrasubstituted zinc phthalocyanine (3) was synthesized. Upon addition of potassium Iodide with PS, the PS exhibited significant photodynamic activity with 5-6 logs reduction in bacterial load was achieved.

1,4-Fluoroamination of 1,3-Enynes en Route to Fluorinated Allenes.

The regioselective synthesis of fluorinated allenes via a metal-free 1,4-fluoroamination of 1,3-enynes is presented. This method employs commercially available N-fluorobenzenesulfonimide serving as both the nitrogen source and the fluorine source, affording access to various tetrasubstituted allenes in a straightforward and atom-economic pathway. Preliminary mechanistic studies and theoretical studies revealed that this reaction might undergo an intimate ion-pair mechanism.

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes.

A copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ, making this protocol operationally simple. The Cu(I) catalyst not only participates in the alkyl diacyl peroxides decomposition to afford alkyl azides but also catalyzes the subsequent CuAAC reaction to produce the 1,2,3-triazoles.

2'-Aryl and 4'-arylidene substituted pyrazolones: As potential α-amylase inhibitors.

Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 ±â€¯0.16 µM to 2.38 ±â€¯0.09 µM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ±â€¯0.26 µM). A number of derivatives including 8-12 (IC50 = 1.68 ±â€¯0.1 µM to 1.97 ±â€¯0.07 µM) and 14-16 (IC50 = 1.61 ±â€¯0.16 µM to 1.93 ±â€¯0.07 µM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.

DNA physical interaction mediated b-lymphoma treatment offered by tetra benzimidazole-substituted zinc (ii) phthalocyanine derivative.

Role of heterocyclic compounds with nitrogen substitution in therapeutic frontiers is well established. The efforts made in this study are directed to dissect the biological significance of benzimidazole-substituted zinc phthalocyanine derivative. Its capacity to act as an anticancer agent against the 2 B-lymphoma cell lines (low-grade and high-grade malignancy) was found out by recording florescence using Alamar blue dye. Further cytotoxic effect at the DNA level was analyzed by performing agarose gel electrophoresis. Molecular docking studies made mechanistic details crystal clear by showing potential dual binding modes employed for interaction with DNA that include minor groove binding and intercalation between bases. This advocates this derivative as potential anticancer agent and deserves further rounds of mechanistic study for its final journey to serve as a marketed drug.

Unprecedented chemosensing behavior of novel tetra-substituted benzimidazole zinc(II) phthalocynine for selective detection of Bi3+ ion: Synthesis, characterization and ROS generation.

In this work, synthesis of novel symmetrical 4-(2-bromo-4-(5-bromo-1H-benzo[d] imidazol-2-yl) phenoxy) tetra substituted zinc phthalocyanine has been reported. The novel benzimidazole zinc phthlocynine compound (3) has been characterized by MALDI-TOF MS, FT-IR, UV-vis, and 1H NMR spectroscopy. This new compound 3 displayed excellent selectivity towards Bi3+ ion in the presence of other competitive ions including Ca2+, Cd2+, Co2+ Cu2+, Fe3+, Hg2+, Sn2+, Mg2+, Na+, Ni2+ and Pb2+ respectively. Upon addition of Bi3+ into the solution of compound 3 in DMSO, dramatic change was observed in the Q- and the B-bands in UV-visible spectra as a result of donor acceptor interactions. Reactive oxygen species (ROS) were also studied using 2,7-dichlorofluorescin diacetate (DCFH-DA) a fluorescent probe which is converted to highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This property of non-aggregating zinc phthalocyanine is promising as a photosensitizer in photodynamic therapy of cancer.

Syntheses of 4,6-dihydroxypyrimidine diones, their urease inhibition, in vitro, in silico, and kinetic studies.

A library of 4,6-dihydroxypyrimidine diones (1-35) were synthesized and evaluated for their urease inhibitory activity. Structure-activity relationships, and mechanism of inhibition were also studied. All compounds were found to be active with IC50 values between 22.6±1.14-117.4±0.73µM, in comparison to standard, thiourea (IC50=21.2±1.3µM). Kinetics studies on the most active compounds 2-7, 16, 17, 28, and 33 were performed to investigate their modes of inhibition, and dissociation constants Ki. Compounds 2, 3, 7, 16, 28, and 33 were found to be mixed-type of inhibitors with Ki values in the range of 7.91±0.024-13.03±0.013µM, whereas, compounds 4-6, and 17 were found to be non-competitive inhibitors with Ki values in the range of 9.28±0.019-13.05±0.023µM. In silico study was also performed, and a good correlation was observed between experimental and docking studies. This study is continuation of our previously reported urease inhibitory activity of pyrimidine diones, representing potential leads for further research as possible treatment of diseases caused by ureolytic bacteria.

Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast α-glucosidase.

Inhibition of α-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[2,3-c] pyrazoles (1-35) were synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast α-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (Ki=9.75±0.07, 46±0.0001, and 69.16±0.01µM, respectively), compound 22 is a competitive inhibitor (Ki=190±0.016µM), while 33 was an uncompetitive inhibitor (Ki=45±0.0014µM) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of α-glucosidase enzyme for further investigation as anti-diabetic agents.

Crystal structure of 2-[2-(benz-yloxy)benzyl-idene]malono-nitrile.

In the title benzyl-idenemalono-nitrile derivative, C17H12N2O, the dihedral angles between the central benzene ring and the Y-shaped C=C(CN)2 group (r.m.s. deviation = 0.006 Å) and the terminal benzene ring are 12.72 (8) and 37.60 (11)°, respectively. The Car-O-Csp (3)-Car torsion angle is -174.52 (13)° and the major twist between the aromatic rings occurs about the Csp (3)-Car bond. Weak aromatic π-π stacking [centroid-centroid separation = 3.7784 (13) Å; slippage = 1.21 Å] between inversion-related pairs of the central benzene rings is observed in the crystal.

Crystal structure of 6-amino-4-(3-bromo-4-meth-oxy-phen-yl)-3-methyl-2,4-di-hydro-pyrano[2,3-c]pyrazole-5-carbo-nitrile dimethyl sulfoxide monosolvate.

In the pyrazole mol-ecule of the title solvate, C15H13BrN4O2·C2H6OS, the dihedral angle between the benzene ring and the mean plane of the di-hydro-pyrano[2,3-c]pyrazole ring system [r.m.s deviation = 0.031 (2) Å] is 86.71 (14)°. In the crystal, the pyrazole mol-ecules are linked by N-H⋯N hydrogen bonds, forming a layer parallel to (10-1). The pyrazole and dimethyl sulfoxide mol-ecules are connected by an N-H⋯O hydrogen bond.