Cancer preventive agents 11. Novel analogs of dimethyl dicarboxylate biphenyl as potent cancer chemopreventive agents^†

Total Synthesis and in Vitro Anti-Tumor-Promoting Activities of Racemic Acetophenone Monomers from Acronychia trifoliolata

“…As mentioned above, previous studies have indicated that prenyl-like structures and acetophenone derivatives tend to show potent effects on inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated tumor-promoting activity. vivo, as was previously reported for several natural product derivatives, such as the analogues of dimethyl biphenyldicarboxylate, 13 betulinic acid, 15,24 and coumarins. 16,25 As shown in Table 3, the tested compounds displayed low to moderate cytotoxicity, as shown by high viability (60%) of Raji cells, implying less than 40% growth inhibition, even at a high concentration of TPA (32 nmol, a compound/TPA molar ratio of 1000:1).…”

“…11–16 Thus, compounds 1 – 7 , 18 , 29 , and 30 were evaluated for cancer chemopreventive activity by means of the Epstein–Barr virus early antigen (EBV-EA) activation stimulated by TPA in Raji cells. It has been proven that inhibitory effects on EBV-EA activation correlate well with anti-tumor-promoting activity in vivo, as was previously reported for several natural product derivatives, such as the analogues of dimethyl biphenyldicar-boxylate, 13 betulinic acid, 15,24 and coumarins. 16,25 …”

“…The organic layer was washed with saturated Na 2 CO 3 , H 2 O, and brine, dried over Na 2 SO 4 , and concentrated in vacuo. The residue was chromatographed on silica gel with EtOAc/n-hexane (1:2) to afford 14 (20.0 mg, 69%) as a yellow oil: 1 H NMR (600 MHz, CDCl 3 ) δ 6.33 (1H, s), 5.20 (2H, s), 3.79−3.76 (1H, m), 3.77 (3H, s), 3.49 (3H, s), 2.87 (1H, dd, J = 16.8, 5.4 Hz), 2.65 (1H, dd, J = 17.4, 6.0 Hz), 2.46 (3H, s), 1.75 (1H, d, J = 7.2 Hz), 1.33 (3H, s), 1.31 (3H, s); 13 1-(3,5-Dihydroxy-7-methoxy-2,2-dimethylchroman-8-yl)ethanone. To a solution of 14 (20.0 mg, 0.06 mmol) in anhydrous MeOH (1.5 mL) was added 3 N HCl (0.3 mL), and the mixture was refluxed for 1.0 h under N 2 .…”

“…11,12 In addition, the importance of a prenyl-like functional group was discussed in our previous reports. 13–16 Thus, prenylated acetophenones, such as the acronyculatins, could significantly inhibit the tumor-promoting activities. To confirm the structure elucidation as well as provide sufficient quantities of materials for further bioassays, the total syntheses of racemic acronyculatins 1 – 7 were performed.…”

Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria

“…In vitro antitumor promoting activity measured as the inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells generally correlates well with cancer chemopreventive effects in vivo [21]. This correlation has been verified by many of our previous studies using various natural products derivatives, such as betulinic acid [22,23], dimethyl dicarboxylate biphenyl [24], and coumarins [25,26]. Because the antitumor promoting effects of phenylethylchromones have not been reported previously, selected compounds 2-4 and 7-11 were examined with the EBV-EA activation assay in Raji cells (▶ Table 3).…”