ABSTRACT
A series of triazaspiro[4.5]dec-8-ene benzylidine derivatives containing thiazolidinone ring system (6-18) have been designed, synthesized and their biological activities evaluated as potential epidermal growth factor receptor inhibitors. Among them, 9-amino-2-(4-nitrobenzylidene)-3-oxo-4-phenyl-7-thioxo-1-thia-4,6,8-triazaspiro[4.5]dec-8-ene-10-carbonitrile (18) displayed the most potent inhibitory activity (IC50=6.355 µM). Antiproliferative assay results indicated that compound 18 exhibited moderate antiproliferative activity against MCF-7 cell line in vitro; with GI50 value of 30.6 µM. In addition, compounds 7 and 15 displayed the highest antiproliferative activity at a common GI50 value of 10.8 µM. Docking simulation was performed to determine the probable binding model and to pursuit information regarding the activity of compound 18. Based on the preliminary results, compound 18 could be used as an attractive building block for designing potential epidermal growth factor receptor inhibitors.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Thiazolidines/chemical synthesis , Thiazolidines/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Dimethyl Sulfoxide , Female , Humans , Indicators and Reagents , Magnetic Resonance Spectroscopy , Models, Molecular , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacology , Quantum Theory , Spectrophotometry, Infrared , Structure-Activity RelationshipABSTRACT
This study was performed to investigate the reactivity of melatonin towards various chemical reagents to produce new derivatives of melatonin containing extra- or fused heterocyclic systems such as the imidazoindole derivatives 3, 5, 6, the triazinoindole derivatives 8a, b, the thiadiazoloindole derivative 12, the pyridinoindole derivative 16 and the aminopyrazolomelatonin derivatives 21a, b and 22a, b. The structures of the compounds were established based on the analytical and spectral data. Agonist and antagonist potency of some melatonin derivatives in clonal Xenopus laevis melanophore cells was studied in comparison with melatonin.
Subject(s)
Melatonin/analogs & derivatives , Melatonin/chemistry , Pigments, Biological/chemistry , Animals , Cell Line , Indicators and Reagents , Magnetic Resonance Spectroscopy , Melanophores/drug effects , Melanophores/metabolism , Xenopus laevisABSTRACT
The reaction of epi-androsterone with cyanoacetyl hydrazine (2) gave the hydrazone derivative 3. The reactivity of 3 towards chemical reagents was studied to give pyridine, thiazole and thiophene derivatives.
