ABSTRACT
Angiogenesis inhibition is a key step towards the designing of new chemotherapeutic agents. In a view to preparing new molecular entities for cancer treatment, eighteen 1,2,3-triazole-uracil ensembles 5a-r were designed and synthesized via the click reaction. The ligands were well characterized using 1H-, 13C-NMR, elemental analysis and ESI-mass spectrometry. The in silico binding propinquities of the ligands were studied sequentially in the active region of VEGFR-2 using the Molegro virtual docker. All the compounds produced remarkable interactions and potentially inhibitory ligands against VEGFR-2 were obtained with high negative binding energies. Drug-likeness was assessed from the ADME properties. Cytotoxicity of the test compounds was measured against HeLa and HUH-7 tumor cells and NIH/3T3 normal cells by MTT assay. Compound 5h showed higher growth inhibition activity than the positive control, 5-fluorouracil (5-FU), against both HeLa and HUH-7 cells with IC50 values of 4.5 and 7.7 µM respectively. Interestingly, the compounds 5a-r did not show any cytotoxicity towards the normal cell lines. The results advance the position of substituted triazoles in the area of drug design with no ambiguity.
Subject(s)
Antineoplastic Agents , Cell Proliferation/drug effects , Protein Kinase Inhibitors , Triazoles , Uracil , Vascular Endothelial Growth Factor Receptor-2 , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Dose-Response Relationship, Drug , Drug Design , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Mice , Molecular Structure , NIH 3T3 Cells , Protein Binding , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Structure-Activity Relationship , Triazoles/chemistry , Uracil/chemistry , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitorsABSTRACT
A novel family of tetraaza macrocyclic Cu(II) complexes [CuLX(2)] (where L = N(4) donor macrocyclic ligands) and (X = Cl(-), NO(3) (-)) have been synthesized and characterized by elemental analysis, magnetic moments, IR, EPR, mass, electronic spectra and thermal studies. The magnetic moments and electronic spectral studies suggest square planar geometry for [Cu(DBACDT)]Cl(2) and [Cu(DBACDT)](NO(3))(2) complexes and distorted octahedral geometry to the rest of the ten complexes. The biological activity of all these complexes against gram-positive and gram-negative bacteria was compared with the activity of existing commercial antibacterial compounds like Linezolid and Cefaclor. Six complexes out of twelve were found to be most potent against both gram-positive as well as gram-negative bacteria due to the presence of thio group in the coordinated ligands.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aza Compounds/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Macrocyclic Compounds/pharmacology , Acetamides/pharmacology , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Aza Compounds/analysis , Aza Compounds/chemistry , Cefaclor/pharmacology , Copper/chemistry , Linezolid , Macrocyclic Compounds/analysis , Macrocyclic Compounds/chemistry , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Oxazolidinones/pharmacology , Spectrophotometry, InfraredABSTRACT
With the aim of obtaining novel biologically active compounds, we have synthesized a series of mono, bis-2-o-arylideneaminophenylbenzimidazoles and a second series of corresponding mono, bis-6-arylbenzimidazo[1,2-c]quinazolines respectively. The target benzimidazo[1,2-c]quinazoline compounds were obtained by the condensation of 2-(o-aminophenyl)benzimidazole with mono and di carbonyl compounds, followed by oxidative cyclisation of the resulting mono and bis-2-o-arylideneaminophenylbenzimidazoles.All the products were characterized via IR, (1)H NMR, (13)C NMR, MS and elemental analysis. The antimicrobial activities of all quinazolines against various bacteria and fungi were evaluated. Among the compounds tested IVd, IVe exhibited good antibacterial and antifungal activities while IIIb, IIIc also showed notable antimicrobial activity with reference to standard drugs Ampicillin and Ketoconazole respectively.