4 research outputs found
Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.
Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models
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