Design of selective TACE inhibitors using molecular docking studies: Synthesis and preliminary evaluation of anti-inflammatory and TACE inhibitory activity

Tumor necrosis factor-α (TNF-α) converting enzyme (TACE) has been considered one of the principal therapeutic targets for the treatment of TNF-dependent pathologies. Several TACE inhibitors have been reported, but none of them has been successfully passed to phase II clinical trials. In the present work, we attempted to design highly selective new non-hydroxamate sulfonamide TACE inhibitors. The docking study was performed on one of the crystal structures of TACE, selected based on its resolution and R value, to tackle the flexibility issue of the active site. The results allowed us to distinguish the analogues with a higher binding affinity toward the active site of TACE and to identify the substituent of analogues needed for binding with the surrounding site of the enzyme. Finally the analogues were docked on crystal structures of six different matrix metalloproteinases (MMPs) for a selectivity study of TACE over MMPs. Some of these analogues were synthesized and subjected to preliminary testing for in vivo anti-inflammatory activity and TACE inhibitory activity.     

Convenient Microwave-Assisted Chlorosulfonic Acid-Catalyzed Synthesis of Some Quinazolinones from 2-Phenylindole

Russian Journal of Organic Chemistry - A new convenient method has been developed for the synthesis of quinazolinones from 2-phenyl-1H-indole and substituted amines under catalysis by...     

Higher Dimensional LRS Bianchi Type-I Domain Walls in a Scalar-Tensor Theory of Gravitation

An exact higher dimensional LRS Bianchi type-I cosmological model is obtained in presence of thick domain walls in a scalar tensor theory of gravitation proposed by Saez and Ballester (Phys. Lett. A113:467, 1985). Some physical and kinematical properties of the models are also discussed.     

Greener approach: Ionic liquid [Et3NH][HSO4]-catalyzed multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)oxazolones under solvent-free condition

We have developed simple, greener, safer multicomponent synthesis series of 4-arylidene-2-phenyl-5(4H) oxazolones 4(a-r) catalyzed by Bronsted acid ionic liquid as triethylammonium hydrogen sulfate [Et₃NH][HSO₄] and catalytic amount of acetic anhydride and sodium acetate with excellent yields (90–99%). The protocol offers economical, environmentally benign, solvent-free conditions, and recycle–reuse of the catalyst and easily available starting as benzoyl chloride 1, amino acid 2 and a variety of aldehydes 3. The cyclization followed by condensation of benzoyl chloride, amino acid, and a variety of aldehydes catalyzed by ILs [Et₃NH][HSO₄] and catalytic amount of acetic anhydride and sodium acetate. The final products were confirmed by their characterization data such as FTIR, ¹H-NMR, ¹³C-NMR, Mass, high-resolution mass spectra and were compared with its reported method.     

Einstein-Rosen inflationary Universe in general relativity

Einstein-Rosen inflationary Universe is investigated in the presence of massless scalar field with a flat potential. To get an inflationary Universe, we have considered a flat region in which the potential V is constant. Some physical properties of the model are discussed.     

An efficient multicomponent synthesis and in vitro anticancer activity of dihydropyranochromene and chromenopyrimidine-2,5-diones

A series of dihydropyranochromenes and chromenopyrimidine-2,5-diones having chromene scaffold were synthesized via efficient multicomponent protocol in aqueous β-cyclodextrin. The reaction is free of toxic solvents, operating under mild conditions and allows for ease of product isolation, making it more environmentally friendly. All the synthesized compounds biologically evaluated for their potential inhibitory effect on both cervical cancer cell line (HeLa) and human breast adenocarcinoma cell line (MCF-7). Of these compounds, 4d was found to be the most potent inhibitors of HeLa and MCF-7 demonstrating IC₅₀ values of 19?µM and 7?µM. Compounds 4b, 4e and 4f also shown significantly good in vitro anticancer activity against HeLa and MCF-7 cancer cell lines.     

Microwave-Assisted Copper Slag-Catalyzed Green S-Arylation of Arenethiols with Arylboronic Acids

Russian Journal of Organic Chemistry - Diaryl sulfides have been synthesized in moderate to excellent yield by S-arylation of arenethiols with arylboronic acids using copper slag as a catalyst....     

Green synthesis and inhibitory effect of novel quinoline based thiazolidinones on the growth of MCF-7 human breast cancer cell line by G2/M cell cycle arrest

Research on Chemical Intermediates - Searching for new active molecules against human breast cancer cell line MCF-7, novel quinoline based thiazolidinones has been efficiently synthesized under...     

A Facile Synthesis of Substituted 2‐(5‐(Benzylthio)‐1,3,4‐oxadiazol‐2‐yl)pyrazine Using Microwave Irradiation and Conventional Method with Antioxidant and Anticancer Activities

A series of novel substituted 2‐(5‐(benzylthio)‐1,3,4‐oxadiazol‐2‐yl)pyrazine derivatives ( 6a – n ) were synthesized under microwave irradiation and conventional conditions with less reaction time with good to excellent yields. All the synthesized compounds were screened for antioxidant and anticancer activities. Out of the 14 prepared derivatives, compounds 6f and 6m were most potent and active with antioxidant and anticancer activities, respectively. Also, the developed technique was simple, easy, and less time consuming.     

Glycerol Mediated Synthesis,Biological Evaluation,and Molecular Docking Study of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines as Potent Antitubercular Agents

A series of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines were synthesized through one‐pot four‐component Hantzsch condensation of 1,3‐diphenyl‐1H‐pyrazole‐4‐carbaldehydes, ammonium acetate, dimedone, and alkyl acetoacetate in glycerol as a green reaction medium. The structures of the compounds are verified by spectroscopic methods and screened for their antimicrobial activity against Mycobacterium tuberculosis H37RV strain. Almost all the synthesized derivatives reveal excellent antitubercular activity based on minimum inhibitory concentration. Especially the compounds 5h and 5k exhibit outstanding antitubercular activity with minimum inhibitory concentration 1.6 μg/mL. In addition, molecular docking study of synthesized scaffolds against enoyl‐acyl carrier protein reductase from M. tuberculosis was performed to propose the binding modes.