fosbretabulin and pyrimidine

fosbretabulin has been researched along with pyrimidine* in 2 studies

Other Studies

2 other study(ies) available for fosbretabulin and pyrimidine

Article	Year
Synthesis of N(4)-(substituted phenyl)-N(4)-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells. Bioorganic & medicinal chemistry, 2013, Feb-15, Volume: 21, Issue:4 A series of fourteen N(4)-(substituted phenyl)-N(4)-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI(50) values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [(3)H]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the βIII isotype of tubulin, which have been associated with clinical drug resistance. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site. Topics: Aniline Compounds; Binding Sites; Cell Line, Tumor; Cell Proliferation; Colchicine; Cyclization; Cyclohexanones; Diamines; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indoles; Microtubules; Molecular Docking Simulation; Oxidation-Reduction; Protein Binding; Protein Structure, Tertiary; Pyrimidines; Tubulin Modulators	2013
1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4. European journal of medicinal chemistry, 2008, Volume: 43, Issue:9 Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50<1 microM for L1210 and <10 microM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 microM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Mice; Pyrimidines; Stilbenes	2008

Article

Year

Synthesis of N(4)-(substituted phenyl)-N(4)-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells.

Bioorganic & medicinal chemistry, 2013, Feb-15, Volume: 21, Issue:4

A series of fourteen N(4)-(substituted phenyl)-N(4)-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI(50) values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [(3)H]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the βIII isotype of tubulin, which have been associated with clinical drug resistance. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site.

Topics: Aniline Compounds; Binding Sites; Cell Line, Tumor; Cell Proliferation; Colchicine; Cyclization; Cyclohexanones; Diamines; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Indoles; Microtubules; Molecular Docking Simulation; Oxidation-Reduction; Protein Binding; Protein Structure, Tertiary; Pyrimidines; Tubulin Modulators

2013

1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4.

European journal of medicinal chemistry, 2008, Volume: 43, Issue:9

Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity (IC50<1 microM for L1210 and <10 microM for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 microM, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Mice; Pyrimidines; Stilbenes

2008