• Archives of Pharmacal Research
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• v.8 no.3
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• pp.187-190
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• 1985

A cytotoxic coumarin against L1210 cell was isolated from the unripe fruit of Poncirus trifoliata ($ED_{5}$) = 10.2 $\mu$ g/ml. Its structure was identified as aurapten, 7-geranyloxycoumarin. Hydrolysis of the substance gave umbelliferone and geraniol. Only geraniol showed the cytotoxic activity ($ED_{53}$ = 6.5 $\mu$g/ml) while umbelliferone and its methyl or allyl derivatives were not active.

• Korean Journal of Pharmacognosy
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• v.20 no.4
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• pp.223-226
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• 1989

A cytotoxic sesquiterpene against L1210 cell has been isolated from the root of Curcuma domestica. Its structure was identified as ${\beta}-sesquiphellandrene$. The cytotoxicity-potentiating substance was (+)-ar-turmerone. (+)-ar-Turmerone potentiated the cytotoxicity of ${\beta}-sesquiphellandrene$(5 fold in $ED_{50}$ value) and an unknown sesquiterpene which was isolated from the root as well, and that of aurapten(6.3 fold) isolated from the unripe fruit of Poncirus trifoliata. Moreover, it potentiated the cytotoxic activities of MeCCNU 10 fold and cyclophosphamide 10 fold. Except the fact that all the effective cytotoxic substances possess relatively good lipophilicity, no relationship between structures of the cytotoxic substances and the cytotoxicity-enhancing effect of (+)-ar-turmerone could be observed.

• Korean Journal of Pharmacognosy
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• v.17 no.2
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• pp.168-177
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• 1986

Bioassay-directed isolation has yielded some cytotoxic substances against L1210 cell from the Korean traditional medicine. These include 5,2'-dihydroxy-6,7,8,6'-teramethoxyflavone $(IV,\;scutellaria\;root,\;ED_{50}\;=\;1.7\;{mu}g/ml)$, 7-geranyloxycoumarin $(XXXII,\;poncirus\;fruit,\;10.2\;{mu}g/ml) $and panaxydol $(I,\;white\;ginseng,\;0.03\;{mu}g/ml)$. IV, XXXII and their derivatives were synthesized in the purpose of in vivo tests and for observation of structure-activity relations. Among the flavone derivatives, 5,2',6'-trihydroxy-6,7,8-trimethoxy flavone (XVIII), 5-hydroxy-6,7,8-trimethoxy-6'-benzyloxyflavone (XVII) and 5,8-dihydroxy-6,7-dimethoxyflavone (X) showed the cytotoxicity which has no correlation to the flavone structures. Of the coumarins synthesized, 7,8-dihydroxycoumarin (XXVI), 6-7-dihydroxycoumarin (XXIX) and 6-hydroxy-5,7-dimethoxycoumarin (XXXI) showed considerable activities. Acetylated XXXI has moderate activity $(ED_{50}=17.2\;{mu}g/ml)$. Monobydroxycoumarins or their methyl and allyl ether were inactive. IV inhibits the growth of the solid form of S-180 by 70% at 40 mg/kg and shows T/C of 166% on the ascitic S-180 at 40 mg/kg. It strongly inhibits the activity of the membrane bounded ATPase from L1210 cell. The most cytotoxic fraction of the antitumor materials studied is the one from the trichosanthes root showing $ED_{50}=0. 0003\;{mu}g/ml$ against L1210 cell. This fraction, obtained from ethyl acetate extract, showed T/C of 130 and 135%, on ICR mice bearing S-180 and $BDF_1$ mice bearing L1210 at 10 mg/kg and 7.5 mg/kg, respectively.

• Journal of Haehwa Medicine
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• v.4 no.2
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• pp.309-329
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• 1996

There are the Seven Effect of Drugs and unique processing methods in Chinese traditional medicine. The Seven Effects are single effrect(單行), additive effect(相加, 相須), synergic effect(上乘, 相使), antagonistic effect(相畏, 拮抗), inhibitory effect(相惡), neutralizing effect(相殺) and opposite effect(相反). We are interested in synergic effects of some drugs and components ; Addition of OLDENLANDIA DIFFUSA to Kilkyungtang combanation enhanced the cytotoxic activity of Kilkyungtang against A549 and B16-Fo eells by 20% and 50%, respectively. The Oldenlandia-added kilkyungtang also potentiated the cytotoxicities of mitomycine Cand 5-fluorouracil. ar-tunnerone. isolated from the root of Curcuma longa, potentiated the cytotoxic activity of sesquiphellandrene(isolated from the same root), aurapten(isolated from Aurantii semen)or cyclophosphamide by 10 times. The purpose of the processing(修治) of Chinese grugs is to remove unusable parts of plants and to eliminate toxicities as well as to produse new active components in drugs. On a occasion of study on the anthelmintic drugs against the chinese fluke(Clonorchis sinesis, (肝디스토마), we have observed that the processed mume fruit(鳥梅) possessed a very very potent clonorchicidal effect, while the methanol extract of the non-processed fruit inactive. The active component was isolated from the processed mume and identified as 5-hydroxymethylfurfuryl aldehyde. This substance dose not occur in the immature fruit and was found only in the processed one. Wehave heated the immature fruit in an oven at $90^{\circ}C$ for 52 hrs and found that the heated fruit eame clonorchidal. As demonstrated in these and other example cited in this presentation, the natural products chemistry is contributory to univeiling the drug effect ensued from the processing and the synergic effect of Oriental medical drug combinations, and to rationalization or modernization of the traditional medicine.