Naphthylphenstatins as tubulin ligands: Synthesis and biological evaluation

Apoptosis of Human Burkitt’s lymphoma cells induced by 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077)

“…Downstream events from tubulin binding are believed to be critical events for the generation of apoptosis in the malignant cell. Trimethoxybenzene derivatives are shown to exhibit powerful effects in blocking tubulin polymerization and inhibiting cell proliferation in many reports (Alvarez et al, 2008a;Alvarez et al, 2008b;Lin et al, 1989). Tubulin-disruption induces apoptosis through phosphorylation of Bcl-2 and activating Bax (Doudican et al, 2008;Jiang et al, 1998).…”

“…Many reports demonstrated that a trimethoxybenzene ring (Fragment A) could contribute to block tubulin polymerization by binding to colchicine site of tubulin (Alvarez et al, 2008a;Alvarez et al, 2008b;Lin et al, 1989). Our earlier studies (Miao et al, 2008) also showed that seleno-podophyllotoxin derivatives containing the fragment A could induce apoptosis through Bax pathway.…”

Exploring the size adaptability of the B ring binding zone of the colchicine site of tubulin with para-nitrogen substituted isocombretastatins

“…HPLC analysis were run on a HP-1100 device from Agilent Technologies or a Delta 600 device from Waters instruments, using X-Terra_MS C18 5 mm (4.6 Â 150 mm), X-Terra_MS C8 5 mm (4.6 Â 150 mm), and X-Terra_MS Phenylic 5 mm (4.6 Â 150 mm) columns with watereacetonitrile or wateremethanol gradients. Combretastatin A4 [56] and phenstatin [53] were synthesized following literature protocols. (1,17,21).…”

“…The effects of the synthesized compounds on in vitro tubulin assembly were tested at different concentrations and the IC 50 of those compounds that displayed tubulin polymerization inhibition over 50% at 5 mM were determined as previously described (Table 1) [ 53,54]. All carbazole derivatives (22, 23, 24 and 25), and the pdimethylaminophenyl and p-pyrrolidin-1-ylphenyl isocombretastatins (3 and 19) show TPI IC 50 values better than that of combretastatin A-4 (3.0 mM).…”

Medicinal Chemistry and Chemical Biology of Diketopiperazine-Type Antimicrotubule and Vascular-Disrupting Agents

“…General antimicrotubule agents, such as colchicine, podophyllotoxin, combretastatin, and phenstatin analogues, which recognize the same binding site on β-tubulin as is recognized by (−)-PLH (5), are structurally characterized as having multiple methoxy groups that make marked contributions to their potent antimicrotubule activities [31][32][33][34] ; however, multiple methoxy substitutions of a plinabulin derivative (e.g., compounds 24, 25, 38i, j) displayed low potencies. These results suggested that plinabulin and its derivatives recognized tubulin in a manner that differed from the binding by colchicine and its biological homologues.…”