Fluoroindole chalcone analogues targeting the colchicine binding site of tubulin for colorectal oncotherapy

Structure–Activity Relationship Study of (E)-3-(6-Fluoro-1H-indol-3-Yl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (FC116) Against Metastatic Colorectal Cancers Resistant to Oxaliplatin

“…Compound 25 To sum up, the indole chalcones showed sensitivity to the resistant cell line like nonresistant cell HCT-116. 16 This study again highlighted the importance of the trimethoxy and αmethyl substitutions. The 6-substitutions on the indole-benzyl ring favored the cytotoxicity.…”

“…The synthetic aspects and the activity against unresistant mCRC cell line HCT-116 have been determined in our previous study. 16 The indole moiety of FC77 was unchanged, and the SAR against the resistant cell line HCT-116/L (resistant to oxaliplatin) on the left phenyl group was determined (Table 1). Oxaliplatin was used as a control drug, showing a GI 50 of 5314 nM against HCT-116 and resistant to HCT-116/L with a GI 50 of 77 213 μM.…”

“…Further SAR study generated the discovery of a representative fluoro-substituted indole-chalcone (FC116, Figure 1). 16,18 This compound has demonstrated high potency against HCT116 and CT26 cell lines, with IC 50 values of 4.52 and 18.69 nM, respectively. In HCT116-xenograft mice, FC116 exhibited a tumor growth inhibition rate of 65.96% at a dose of 3 mg/kg, which is much better than paclitaxel (PTX).…”

“…In APC min/+ mice, FC116 showed a significant adenoma number inhibition rate of 76.3%. 16 Additional modifications on the 4-methoxyphenyl group led to a water-soluble compound FC11619 (Figure 1) that achieved tumor growth inhibition rates of 65.3% and 73.4% at doses of 5 and 10 mg/kg/d for 21 d. 18 Therefore, indole-chalcone derivatives should be a kind of privileged compound for anticancer study. However, the efficacy of the series of indole-chalcones against resistance to standard therapies has not been investigated.…”

“…In HCT116-xenograft mice, FC116 exhibited a tumor growth inhibition rate of 65.96% at a dose of 3 mg/kg, which is much better than paclitaxel (PTX). In APC min/+ mice, FC116 showed a significant adenoma number inhibition rate of 76.3% . Additional modifications on the 4-methoxyphenyl group led to a water-soluble compound FC11619 (Figure ) that achieved tumor growth inhibition rates of 65.3% and 73.4% at doses of 5 and 10 mg/kg/d for 21 d …”