ABSTRACT
Synthesis of 3-(4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)piperazin-1-yl) benzoisothiazole derivatives (5a-i), which constitute a new class of isoxazolines, has been accomplished in regio-selective manner. These derivatives have been prepared by employing the reaction between substituted aldoximes (4a-i) and 3-(4-Allylpiperazin-1-yl) benzoisothiazole in presence of chloramine-T which afforded in good yields. These compounds were screened for cytotoxic activity on tumor cells. Four among the nine synthesized compounds were found to exhibit potent cytotoxic and antineoplastic activities in comparison to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in mammalian cancer cells. The rest of the derivatives showed moderate activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Isoxazoles/chemical synthesis , Isoxazoles/pharmacology , Piperazines/chemistry , Thiazoles/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Chemistry Techniques, Synthetic , Drug Design , Humans , Isoxazoles/chemistry , Time FactorsABSTRACT
In the present study a series of O-substituted pyrazoles 7(a-f) and N-substituted pyrazoles 9(a-f) were synthesized via phase-transfer catalyzed reaction of ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate 5 with various oxygen and nitrogen containing compounds in presence of tetrabutylammonium bromide (TBAB) in THF. The compound 5 was obtained by the efficient bromination with N-bromosuccinimide (NBS) in presence of a catalytic amount of azoiso-bis-butyro nitrile (AIBN) in refluxing CCl4. The synthesized compounds were evaluated for their in vitro antimicrobial and antidiabetic activity and were compared with standard drugs. Among the synthesized compounds, compound 9b emerged as an excellent antimicrobial and antidiabetic agent. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods.
Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Pyrazoles/chemistry , Anti-Infective Agents/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , Drug Evaluation, Preclinical/methods , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Hypoglycemic Agents/chemical synthesis , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Docking Simulation , Structure-Activity Relationship , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/chemistry , alpha-Amylases/metabolism , alpha-Glucosidases/metabolismABSTRACT
A series of piperamide derivatives (8a-j) was synthesized with various substituted piperidine and piperazine compounds. The prepared compounds were evaluated for antibacterial activity against gram-positive and gram-negative bacteria and antifungal activity by disc diffusion method. The antioxidant activity of the compounds was evaluated by DPPH and superoxide radical scavenging method and antidepressant activity using forced swim and tail suspension behavioral despair tests in mice. The compounds 8a, 8b and 8c were investigated for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory property. Some of the test compounds were active in forced swim test (FST) and tail suspension test (TST). Compounds 8a and 8b showed a significant effect, when compared to standard drug, clorgyline.
Subject(s)
Amides/chemistry , Antidepressive Agents/chemical synthesis , Antioxidants/chemical synthesis , Piperazines/chemistry , Piperidines/chemistry , Amides/chemical synthesis , Amides/pharmacology , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antidepressive Agents/chemistry , Antidepressive Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antioxidants/chemistry , Behavior, Animal/drug effects , Candida albicans/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Mice , Monoamine Oxidase/chemistry , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , PiperazineABSTRACT
Precursors of podophyllotoxin were synthesized and screened for their antibacterial activity. The results proved that ethyl-2-(3'-methyl-4'-methoxybenzoyl)-3-(4â³ methoxyphenol)-cyclopropane-1-carboxylic acid and Ethyl-2-(3'-methyl-4'-methoxybenzyol-3-1 3â³, 4â³-dimethoxyphenyl)-cyclopropane-carboxylic acid have significant antibacterial activity against Citrobacter sp., Escherchia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella sonnei and Streptococcus faecalis. The activity is lower than Ciprofloxacin and equal to Gentamicin and more than Penicillin and Streptomycin.
