Song, Ming-Yu; Cao, Chen-Yu; He, Qiu-Rui; Dong, Qing-Miao; Li, Ding; Tang, Jiang-Jiang; Gao, Jin-Ming published the artcile< Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions>, Application In Synthesis of 53581-86-5, the main research area is dihydrofuran dihydroisoxazole isocombretastatin analog preparation tubulin polymerization inhibitor; Combretastatin-4; Dihydrofuran; Dihydroisoxazole; Isocombretastatin-4; Tubulin polymerization inhibitors; [3+2] reactions.
[3+2] Reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogs of isoCA-4 were synthesized as inhibitors of tubulin polymerization Among them, compound 6g (5-(3-(4-chlorophenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroisoxazol-5-yl)-2-methoxyphenol) was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47 μM, and compound 5p ((5-(3-hydroxy-4-methoxyphenyl)-2-phenyl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydrofuran-3-yl)(phenyl)methanone) exhibted highest activity on HeLa cells with IC50 vaule of 2.32 μM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochem. studies and cell cycle distribution anal. indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, mol. docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.
Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 53581-86-5 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO2, Application In Synthesis of 53581-86-5.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics