1070195-79-7Relevant articles and documents
A fluorine scan of a tubulin polymerization inhibitor isocombretastatin A-4: Design, synthesis, molecular modelling, and biological evaluation
Naret, Timothée,Bignon, Jér?me,Bernadat, Guillaume,Benchekroun, Mohamed,Levaique, Helene,Lenoir, Christine,Dubois, Joelle,Pruvost, Alain,Saller, Fran?ois,Borgel, Delphine,Manoury, Boris,Leblais, Veronique,Darrigrand, Romain,Apcher, Sébastien,Brion, Jean-Daniel,Schmitt, Etienne,Leroux, Frédéric R.,Alami, Mouad,Hamze, Abdallah
, p. 473 - 490 (2017/12/07)
A novel series of tubulin polymerization inhibitors, based on fluorinated derivatives of isocombretastatin A-4 was synthesized with the goal of evaluating the effect of these compounds on the proliferative activity. The introduction of fluorine atom was performed on the phenyl ring or at the linker between the two aromatic rings. The modification of isoCA-4 by introduction of difluoromethoxy group at the para-position (3i) and substitution of the two protons of the linker by two fluorine atoms (3m), produced the most active compounds in the series, with IC50 values of 0.15–2.2 nM (3i) and 0.1–2 nM (3m) respectively, against a panel of six cancer cell lines. Compounds 3i and 3m had greater antiproliferative activity in comparison with references CA-4 or isoCA-4, the presence of fluorine group leads to a significant enhancement of the antiproliferative activity. Molecular docking studies indicated that compounds 3i and 3m occupy the colchicine binding site of tubulin. Evaluation of cytotoxicity in Human noncancer cells indicated that the compounds 3i and 3m were practically ineffective in quiescent peripheral blood lymphocytes, and may have a selective antiproliferative activity against cancer cells. Analyses of cell cycle distribution, and morphological microtubules organization showed that compound 3m induced G2/M phase arrest and, dramatically disrupted the microtubule network.
Discovery of Isoerianin Analogues as Promising Anticancer Agents
Messaoudi, Samir,Hamze, Abdallah,Provot, Olivier,Treguier, Bret,RodrigoDeLosada, Jordi,Bignon, Jerome,Liu, Jian-Miao,Wdzieczak-Bakala, Joanna,Thoret, Sylviane,Dubois, Joelle,Brion, Jean-Daniel,Alami, Mouad
scheme or table, p. 488 - 497 (2011/12/22)
The cytotoxic activity of a series of 23 new isoerianin derivatives with modifications on both the A and B rings was studied. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. The most cytotoxic compound, isoerianin (3), strongly inhibits tubulin polymerization in the micromolar range. Moreover, isoerianin leads to G2/M phase cell-cycle arrest in H1299 and K562 cancer cells, and strongly induces apoptosis. Isoerianin also disrupts the vessel-like structures formed by human umbilical vein endothelial cells (HUVECs) invitro, suggesting that this compound may act as a vascular disrupting agent. It clearly appears that in this compound series, the 1,1-ethane bridge encountered in isoerianin derivatives can replace the 1,2-ethane bridge of natural erianin with no loss of activity. This reinforces the bioisosteric replacement approach in the combretastatin series previously reported by our research group.
ISO CA-4 AND ANALOGUES THEREOF AS POTENT CYTOTOXIC AGENTS INHIBITING TUBULINE POLYMERIZATION
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Page/Page column 18, (2010/06/14)
The invention relates to a compound of the formula (I) in which: R1, R2 and R3 are independently a methoxy group optionally substituted by one or more fluorine atoms; R4 is a hydrogen atom; R5 and Rs
