| This dissertation project was initiated as part of an investigation directed toward the discovery of new cancer chemopreventive agents from plants, and two species were chosen for detailed study. The petroleum ether and ethyl acetate-soluble extracts of the stem bark of Pongamia pinnata (L.) Pierre (Leguminosae), collected in West Irian (Irian Jaya), Indonesia, showed significant inducing activity in the quinone reductase assay (CD <2.5 μg/mL and <3.5 μg/mL, respectively). Bioassay-guided fractionation of these extracts using cultured Hepa 1c1c7 mouse hepatoma cells in a quinone reductase induction assay led to the isolation of four new flavanone derivatives [(2 S)-5,7-dimethoxy-8-(2S-hydroxy-3-methyl-3-butenyl)-3 ′,4′-methylenedioxyflavanone, (2 S)-5,7-dimethoxy-8-(2S-hydroxy-3-methyl-3-butenyl)-flavanone, (2S)-5,7-dimethoxy-8-(2R-hydroxy-3-methyl-3-butenyl)-flavanone, and (2S)-5,7-dimethoxy-8-formyl-flavanone], one new flavone [5-methoxy-3″,4″-diacetoxy-(3 ″,4″-dihydro)-2″,2 ″-dimethylpyrano-(7,8:5″,6″ )-flavone], and one new chalcone [(7-O-methylpraecansone B)] together with 13 known compounds of the alcohol [(1-hexacosanol)], fatty acid [(octadecanoic acid)], flavonoid [candidin, candidone, 3′ -methoxypongapin, 5-methoxy-3′,4′ -methylenedioxy-2″,2″-dimethylpyrano-(7,8:5 ″,6″)-flavone, pongapinone A, pongapinone B, and praecansone B], sterol [(stigmasterol 3-O-β- D-glucopyranoside)], and terpenoid [(betulinic acid, α-cadinol, lupenone, and lupeol)] types. Three of the new compounds [(2S)-5,7-dimethoxy-8-formyl-flavanone, (2S)-5,7-dimethoxy-8-(2S-hydroxy-3-methyl-3-butenyl)-flavanone, and 7-O-methylpraecansone B], and seven of the known compounds [candidin, candidone, 3′-methoxypongapin, 5-methoxy-3 ′,4′-methylenedioxy-2″,2 ″-dimethylpyrano-(7,8:5″,6″ )-flavone, pongapinone A, pongapinone B, and praecansone B] exhibited induction activity in the quinone reductase assay, while the other nine isolates were inactive (IC50 > 5 mg/mL).; The petroleum ether and ethyl acetate-soluble extracts of the stem bark of Arbutus unedo L. (Ericaceae), a second species studied that was collected in Turkey, showed significant inhibition of transformation of the JB6 murine epidermal cell line assay (IC50 0.9 μg/mL and 3.5 μg/mL, respectively). Bioassay-guided fractionation of these extracts using the JB6 murine epidermal cell assay as a monitor, led to the isolation of one new sterol derivative [(7β-hydroxy-4-stigmasten-3-one)], along with nine known compounds of the flavan [(−)-catechin], sterol [β-sitosterol and 6β-hydroxy-4-stigmasten-3-one], and triterpenoid [α-amyrin acetate, betulin, betulinic acid, lupeol, platanic acid, and pomolic acid 3-acetate] types. One of the known compounds, pomolic acid 3-acetate, exhibited significant activity in the JB6 cell assay, while the other isolates were inactive (IC50 > 20 mg/mL). The new compound, 7β-hydroxy-4-stigmasten-3-one, and three of the known compounds [α-amyrin acetate, lupeol, and (−)-catechin] were found to exhibit activity in the COX-2 assay, while the other isolates were inactive (IC50 > 100 mg/mL).; The structures... |
