Synthesis and antitumor activity of benzophenone compound.

Seven benzophenone compounds were synthesized in one or two steps, then their antitumor activity was evaluated. The total yields ranged from 9% to 44%. Compounds 3c-5c exhibited obvious antitumor activity. Among them, compounds 3c and 4c exhibited excellent and broad-spectrum antitumor activity. Compound 3c exhibited much stronger inhibitory activities against fourteen cancer cells than cisplatin. In particular, compound 3c exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than Taxol, with a half maximal inhibitory concentration (IC50) of approximately 0.111 µM. These results demonstrated that compounds 3c, 4c and 5c were very promising antitumor leads for further structural modification.

Syntheses of xanthone derivatives and their bioactivity investigation.

Sixteen substituted 1-hydroxy-3-methylxanthones were synthesized in one step. The yields ranged from 33 to 76%. Then, the antitumor, antioxidant, anti-tyrosinase, anti-pancreatic lipase, and antifungal activities of compounds 1-16 were evaluated. Compounds 10-12 and 14 inhibited tyrosinase and pancreatic lipase activity to a certain extent, respectively. Compound 16 exhibited obvious cytotoxicity against fifteen cancer cells, moderate antioxidant activity, and moderate inhibitory activity against Candida albicans. In particular, compound 16 exhibited strong inhibitory activity against A-549 and A549/Taxol cells. These results demonstrated that compounds 10-12, 14, and 16 are promising leads for further structural modification.[Formula: see text].

Efficient synthesis, and antitumor and antioxidant activities of polyhydroxybenzophenone.

Five polyhydroxybenzophenones were synthesized, then their antitumor and antioxidant activities were evaluated. Compounds 1-3 and 5 exhibited obvious antitumor activity. Among them, compounds 1 and 2 exhibited stronger cytotoxicity against hepatocarcinoma SMMC-7721 cells than cisplatin, with half maximal inhibitory concentrations (IC50) of approximately 3.86 and 5.32 µM, respectively. Compounds 1, 2, and 3 exhibited stronger antioxidant activity than trolox, with IC50 values of 11.15, 10.15, and 8.91 µM, respectively, and the antioxidant mechanism and strength of all compounds were further verified using computational chemistry. These results demonstrated that compounds 1-3 and 5 were very promising leads for further structural modification.

Synthesis and antitumor, antityrosinase, and antioxidant activities of xanthone.

Ten substituted 1,3-dihydroxyxanthones were synthesized in one step. The yields ranged from 40 to 76%. Compounds 8-10 were first reported. Next, the compounds' in vitro anti-proliferative activities against nine human cancer cell lines, antityrosinase, and antioxidant activities were evaluated. Compounds 1, 4, 6-7, and 9-10 exhibited enhanced cytotoxicity against certain cancer cells. Compounds 2, 8, 9, and 10 inhibited tyrosinase activity to a certain extent. In addition, compound 4 exhibited the best antioxidant activity, which was consistent with theoretical calculations. These results demonstrated that compounds 1-2, 4, and 6-10 were promising leads for further investigation.

Metabolic activation of pradefovir by CYP3A4 and its potential as an inhibitor or inducer.

Metabolic activation of pradefovir to 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was evaluated by using cDNA-expressed CYP isozymes in portal vein-cannulated rats following oral administration and in human liver microsomes. The enzyme induction potential of pradefovir was evaluated in rats following multiple oral dosing and in primary cultures of human hepatocytes. The results indicated that CYP3A4 is the only cDNA-expressed CYP isozyme catalyzing the conversion of pradefovir to PMEA. Pradefovir was converted to PMEA in human liver microsomes with a K(m) of 60 microM, a maximum rate of metabolism of 228 pmol/min/mg protein, and an intrinsic clearance of about 359 ml/min. Addition of ketoconazole and monoclonal antibody 3A4 significantly inhibits the conversion of pradefovir to PMEA in human liver microsomes, suggesting the predominant role of CYP3A4 in the metabolic activation of pradefovir. Pradefovir at 0.2, 2, and 20 microM was neither a direct inhibitor nor a mechanism-based inhibitor of CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 in human liver microsomes. In rats, the liver was the site of metabolic activation of pradefovir, whereas the small intestine did not play a significant role in the metabolic conversion of pradefovir to PMEA. Daily oral dosing (300 mg/kg of body weight) to rats for 8 days showed that pradefovir was not an inducer of P450 enzymes in rats. Furthermore, pradefovir at 10 microg/ml was not an inducer of either CYP1A2 or CYP3A4/5 in primary cultures of human hepatocytes.