ABSTRACT
A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.
Subject(s)
Antineoplastic Agents/chemical synthesis , Nitriles/chemical synthesis , Pyrimidines/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Nitriles/pharmacology , Pyrimidines/pharmacology , Structure-Activity RelationshipABSTRACT
A novel series of 2-(3-fluoro-4-nitrophenoxy)-N-phenylacetamide compounds were designed, synthesized and in vitro assessed for their antitubercular activities by a microdilution method. All the novel derivatives exerted potent or moderate active against M. tuberculosis H37Rv, with MIC values ranging from 4 to 64 µg/mL. The most potent derivative 3m showed an identical MIC value of 4 µg/mL for both M. tuberculosis H37Rv and rifampin-resistant M. tuberculosis 261. It demonstrated no inhibitory effects against six different tumor cell lines by a MTT assay and had a good safety profile in a vero cell line, providing a good lead for subsequent optimization in search of novel affordable antitubercular agents.
Subject(s)
Acetanilides/chemical synthesis , Acetanilides/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Animals , Cell Line, Tumor , Chlorocebus aethiops , HCT116 Cells , HeLa Cells , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Rifampin/pharmacology , Vero CellsABSTRACT
In the mol-ecular structure of the title compound, C(15)H(11)NO(4)S(3), the 1,2,4-dithia-zolone and central benzene rings are approximately coplanar, making a dihedral angle of 3.08â (7)°. The central benzene ring and the 4-methyl-benzene ring subtend a dihedral angle of 57.47â (8)°. In the crystal, π-π stacking occurs between the central benzene ring and the 1,2,4-dithia-zolone ring of adjacent mol-ecules, which are aligned almost parallel, the centroid-centroid distance being 3.555â (7)â Å.
