26279-89-0Relevant academic research and scientific papers
Effects on tubulin polymerization and down-regulation of c-Myc, hTERT and VEGF genes by colchicine haloacetyl and haloaroyl derivatives
Marzo-Mas, Ana,Falomir, Eva,Murga, Juan,Carda, Miguel,Marco, J. Alberto
, p. 591 - 600 (2018/05/15)
Several colchicine analogues in which the N-acetyl residue has been replaced by haloacetyl, cyclohexylacetyl, phenylacetyl and various aroyl moieties have been synthesized. The cytotoxic activities of the synthesized compounds have been measured on three tumor cell lines (HT-29, MCF-7 and A549) and on one non-tumor cell line (HEK-293). These compounds exhibit high antiproliferative activities at the nanomolar level, in many cases with a higher potency than colchicine itself. Some of the compounds, particularly the haloacetyl derivatives, inhibit the polymerization of tubulin in a similar manner as colchicine. As regards the cell cycle, the most active compounds are the chlorobenzoyl and bromobenzoyl derivatives, which cause cell cycle arrest at the G2/M phase when tested at 20 nM, and the bromoacetyl derivative, which arrests the cell cycle at 15 nM. In addition, these colchicine derivatives have shown fairly active downregulating the expression of the c-Myc, hTERT and VEGF genes, as well as VEGF protein secretion, at very low concentrations.
Glycopeptide dendrimer colchicine conjugates targeting cancer cells
Johansson, Emma M.V.,Dubois, Jo?lle,Darbre, Tamis,Reymond, Jean-Louis
experimental part, p. 6589 - 6597 (2010/10/04)
Screening of a 65,536-member one-bead-one-compound (OBOC) combinatorial library of glycopeptide dendrimers of structure ((βGal)n +1X8X7X6X5) 2DapX4X3X2X1(β-Gal) m (βGal = β-galactosyl-thiopropionic acid, X8-1= variable amino acids, Dap = l-2,3-diaminopropionic acid, n, m = 0, or 1 if X8= Lys resp. X1= Lys) for binding of Jurkat cells to the library beads in cell culture, resynthesis and testing lead to the identification of dendrimer J1 (βGal-Gly-Arg-His-Ala)2Dap-Thr- Arg-His-Asp-CysNH2 and related analogues as delivery vehicles. Cell targeting is evidenced by FACS with fluorescein conjugates such as J1F. The colchicine conjugate J1C is cytotoxic with LD50 = 1.5 μM. The β-galactoside groups are necessary for activity, as evidenced by the absence of cell-binding and cytotoxicity in the non-galactosylated, acetylated analogue AcJ1F and AcJ1C, respectively. The pentagalactosylated dendrimer J4 βGal4(Lys-Arg-His-Leu)2Dap-Thr-Tyr-His-Lys(βGal) -Cys) selectively labels Jurkat cell as the fluorescein derivative J4F, but its colchicine conjugate J4C lacks cytotoxicity. Tubulin binding assays show that the colchicine dendrimer conjugates do not bind to tubulin, implying intracellular degradation of the dendrimers releasing the active drug.
Inhibition of mitosis by glycopeptide dendrimer conjugates of colchicine
Lagnoux, David,Darbre, Tamis,Schmitz, M. Lienhard,Reymond, Jean-Louis
, p. 3941 - 3950 (2007/10/03)
Glycopeptide dendrimers have been prepared bearing four or eight identical glycoside moieties at their surface (β-glucose, α-galactose, α-N-acetyl-galactose, or lactose), natural amino acids within the branches (Ser, Thr, His, Asp, Glu, Leu, Val, Phe), 2,3-diaminopropionic acid as the branching unit, and a cysteine residue at the core. These dendrimers have been used as drug-delivery devices for colchicine. Colchicine was attached to the dendrimers at the cysteine thiol group through a disulfide or thioether linkage. The biological activities of the glycopeptide dendrimer conjugates were evaluated in HeLa tumor cells and non-transformed mouse embryonic fibroblasts (MEFs). The concentrations of glycopeptide dendrimer drug conjugates required to achieve inhibition of cell proliferation by interference with the tubulin system were found to be higher (IC50 > 1 μm) compared to the required colchicine concentration. On the other hand, the glycopeptide dendrimer conjugates inhibited the proliferation of HeLa cells 20-100 times more effectively than the proliferation of MEFs. In comparison, non-glycosylated dendrimers and colchicine itself showed a selectivity of 10-fold or less for HeLa cells.
