Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents

Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure–activity relationship studies demonstrate that the introduction of <i>p</i>-<i>N</i>, <i>N</i>-dialkyl/diaryl, and <i>o</i>-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. <i>In vivo</i> tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound <b>27</b> exhibits single agent activity in inhibiting the tumor growth