1352545-29-9Relevant articles and documents
Synthesis and evaluation of 1,5-disubstituted tetrazoles as rigid analogues of combretastatin A-4 with potent antiproliferative and antitumor activity
Romagnoli, Romeo,Baraldi, Pier Giovanni,Salvador, Maria Kimatrai,Preti, Delia,Aghazadeh Tabrizi, Mojgan,Brancale, Andrea,Fu, Xian-Hua,Li, Jun,Zhang, Su-Zhan,Hamel, Ernest,Bortolozzi, Roberta,Basso, Giuseppe,Viola, Giampietro
, p. 475 - 488 (2012/02/16)
Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. Two series of 1,5-diaryl substituted 1,2,3,4-tetrazoles were concisely synthesized, using a palladium-catalyzed cross-coupling reaction, and identified as potent antiproliferative agents and novel tubulin polymerization inhibitors that act at the colchicine site. SAR analysis indicated that compounds with a 4-ethoxyphenyl group at the N-1 or C-5 position of the 1,2,3,4-tetrazole ring exhibited maximal activity. Several of these compounds also had potent activity in inhibiting the growth of multidrug resistant cells overexpressing P-glycoprotein. Active compounds induced apoptosis through the mitochondrial pathway with activation of caspase-9 and caspase-3. Furthermore, compound 4l significantly reduced in vivo the growth of the HT-29 xenograft in a nude mouse model, suggesting that 4l is a promising new antimitotic agent with clinical potential.
