• Bulletin of the Korean Chemical Society
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• v.8 no.1
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• pp.39-45
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• 1987

Daunomycin, an anthracycline antibiotic, has been found to inhibit virus multiplication and shows considerable activity against tumors. Its activity may be varied by conformational changes of daunomycin. The conformational changes are come from the pucker of D-ring and variation of environments. We have carried out conformational analyses by using empirical potential function. We found that when daunomycin is hydrated or bound to $Mg^{2+}$ ion, the minimum conformer of each state is altered from ${\alpha}$ conformer to ${\beta}$ conformer through the pathway having four local minima. Our calculated results are in good agreements with those of X-ray crystallography and biological experiments, in which metal ion inhibits the binding of daunomycin to DNA.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1359-1363
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• 2006

Novel anthracycline analogues 2-9 as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium lactate, and stearic acid, respectively. Compounds 3-5 and 7-9 were prepared by the reaction of either daunomycin (1a) or doxorubicin (1b) with L-lactic and stearic acids in the presence of EDCI/PP reagents.

• Bulletin of the Korean Chemical Society
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• v.22 no.9
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• pp.963-968
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• 2001

New anthracycline analogues 2-9 as potential anticancer agents have been synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2 and 6 were prepared by the nucleophilic displacement type esterification of 14-bromodaunomycin (1c) with N-benzoyl-(2R,3S)-phenylisoserine and L-pyroglutamic acid in triethyl-amine, respectively. Compounds 3, 7 and 4, 8 were prepared by the reaction of either daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP. Compounds 5, 9 were obtained from 1b by reaction with 2.2 equivalents of the corresponding acids in the same manner. The cytotoxic activities of the analogues in comparison with adrimycin on cultured SNU-16 and MCF7 cell were described.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.249-254
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• 2005

Multidrug resistance (MDR) of cancer cells is, at least in part, associated with the overexpression of P-glycoprotein (P-gp). Many studies have demonstrated that natural compounds obtained from fruits, vegetables, teas and medicinal plants may modulate P-gp activity. The objective of the present investigation was to examine the effect of seven natural compounds on the P-gp activity in human uterine sarcoma cell line, MES-SA/DX5. Daunomycin uptake was significantly increased by biochanin A and silymarin (p<0.0001) whereas it was reduced by morin (p<0.01). The efflux of daunomycin from the cells was significantly inhibited by biochanin A, morin, cephalotaxine, berberine (p<0.05) and silymarin (p<0.0001). Biochanin A, berberine and silymarin significantly decreased $IC_{50}$ value of daunomycin (p<0.05) while morin increased it (p<0.05). These results suggest that some natural compounds such as biochanin A and silymarin may inhibit P-gp function and can be developed as MDR reversing agents to improve the efficacy of chemotherapeutic drugs when administered concomitantly.

• The Korean Journal of Food And Nutrition
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• v.16 no.4
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• pp.303-309
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• 2003

This study was performed to investigate the antimutagenic and antioxidative activities of pine pollen with respect to the microbial mutation induced by various mutagens such as 1-NP, daunomycin, 2-NF, MNNG, NaN$_3$, 4NQO, 4-NOPD, AFB$_1$, Trp-P-1, 2-AF and oxidative mutagens such as t-BOOH, H$_2$O$_2$. Pine pollen, originally extracted with hexane, was reextracted with 70% methanol. The results obtained using the methanol extract, in terms of the antimutagenicity observed in relation to ten kinds of mutagens, showed that it exhibited 17.8, 82.2 and 80.9% inhibitory effects against daunomycin, AFB$_1$, and Trp-P-1, respectively, in Salmonella. typhimurium TA98 and a 72.3% inhibitory effect against AFB$_1$in S. tyPhimurium TA100. In terms of the antimutagenicity exhibited in relation to t-BOOH, a 72.3% inhibitory effect was observed, but no antimutagenicity was observed in relation to the other mutagens and strains. The methanol extract was further fractionated by chloroform, ethyl acetate, n-butanol. In S. typhimurium TA98, the chloroform(150 $\mu\textrm{g}$/plate) fraction showed strong antimutagenic effects of 55.6%, 93.7% and 93.5%, while the ethyl acetate(100 $\mu\textrm{g}$/plate) fraction showed 11.4%, 74.3% and 85.2% in relation to the mutagenicity induced by daunomycin, AFB$_1$and Trp-P-1, respectively. In S. typhimurium TA100, the chloroform and ethyl acetate fractions showed antimutagenic effects of 95.1% and 62.5%, respectively, on the mutagenicity induced by AFB$_1$. In S. typhimurium TA102, the chloroform fraction showed an antimutagenic effect of 93.6% on the mutagenicity induced by t-BOOH.

• Bulletin of the Korean Chemical Society
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• v.22 no.6
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• pp.581-586
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• 2001

The potential anticancer agents, new anthracycline analogues (2-9) have been synthesized from the glycosides daunomycin (1a) and doxorubicin (1b). Compounds 2 and 6 were prepared by nucleophilic displacement esterification of a 14-bromodauomycin(1c) with sodium or potassium salts of butyric and all trans retinoic acid, respectively. Compounds 3 and 7 were obtained from daunomycin (1a) by direct amidation with a butyric and all trans retinoic acid in the presence of EDCI and PP, respectively. Compounds 4 and 8 were obtained from doxorubicin (1b) by reaction with the corresponding acids in the same manner. Compounds 5 and 9 were prepared from doxorubicin (1b) by acylation with two equivalents of the corresponding acids under the same reaction conditions.

• Bulletin of the Korean Chemical Society
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• v.22 no.6
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• pp.587-592
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• 2001

The potential anticancer agents new anthracycline derivatives (2~9) have been synthesized from daunomycin (1a) and doxorubicin (1b) ad starting materials. Compounds 2 and 6 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a acetylsalicylic and palmitic acid in triethylamine, respectively. Compound 3 and 7 were obtained from daunomycin (1a) by direct amidation with the corresponding acids in the presence of EDCI and PP as esterification regents. Whereas 4 and 8 were prepared by reaction of doxorubicin (1b) with one equivalent of acetylsalicylic and palmitic acid using DCC/DMAP, respectively, 5 and 9 were obtained from 1b by acylation with two equivalents of the corresponding acids using EDCI/PP reagents.

• Natural Product Sciences
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• v.10 no.6
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• pp.268-271
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• 2004

In order to examine their effects on the P-glycoprotein (P-gp) activity in human breast cancer cells, MCF-7/ADR, one hundred Indonesian plant extracts were screened. Among them, the five chloroform extracts of Calotropis gigantea, Curcuma aeruginosa, Merremia mammosa, Sindora sumatrana, and Zingiber cassumunar, showed the most potent P-gp inhibitory activity. When each of these extracts was treated together with the anticancer agent, daunomycin, they increased the cytotoxic activity of daunomycin up to $IC_{50}$ values of less than $6.62\;{\mu}M$, which is a value with a positive control, verapamil. Also, other 15 plant extracts exhibited significant P-gp inhibitory activity with $IC_{50}$ values between 6.62 and $13.20\;{\mu}M$. These prospective samples will be subjected to further laboratory phytochemical investigation to find active principles.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.315-320
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• 2006

Silymarin showed P-glycoprptein(P-gp) inhibitory activity as much as verapamil, a well-known P-gp inhibitor, by decreasing $IC_{50}$ value of daunomycin(DNM)($16.0{\pm}0.7{\mu}M$), increasing the DNM accumulation($224.9{\pm}3.2%$), and decreasing DNM efflux($58.5{\pm}6.7%$), concurrently. In this study, we clarified the mechanism of action of silymarin for P-gp inhibitory function. First, silymarin may bind to the ATP-binding site and thus, prevent ATP hydrolysis. Second, the P-gp inhibitory activity of silymarin is not related to changing the cellular P-gp level. Third, the cytotoxicity of silymarin was increased in the presence of verapamil, reflecting that silymarin is a competent P-gp substrate against verapamil in the P-gp-overexpressed adriamycin-resistant MCF-7 breast cancer(MCF-7/ADR) cells. Conclusively, silymarin had the P-gp inhibitory activity through the action of competent binding to the P-gp substrate-binding site. Therefore, silymarin can be a good candidate for safe and effective MDR reversing agent in clinical chemotherapy by administering concomitantly with anticancer drugs.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.95-99
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• 2004

One mechanism which plays a prominent role in development of multi-drug resistance seen in cancer cells is the over-expression of P-glycoprotein (P-gp). It is known that compounds found in vegetables and fruits not only have anticarcinogenic properties but may also modulate P-gp activity. The effect of some dietary components on efflux of daunomycin (DNM), a P-gp substrate, was examined in P-gp over-expressed human uterine sarcoma cell line, MES-SA/DX5. The efflux of DNM from the cells was significantly inhibited by quercetin and verapamil, but not by 1-naphtyl-isothiocyanate (NITC). The $IC_{50}$ values for DNM in MES-SA/DX5 cells were increased by flavonoids (quercetin and fisetin), but not by NITC after 72 hour incubation with dietary constituents. In conclusion, flavonoids may play a role in the modulation of P­-gp activity in human uterine sarcoma cells.