ABSTRACT
Two series of combretoxazolones including 3,4-diaryloxazolones (6) and 4,5-diaryloxazolones (7) were synthesized and evaluated for cytotoxicity and antitumor activity. Both series showed strong cytotoxicities against a variety of tumor cell lines. Compound 6g exhibited a significant antitumor activity in BDF1 mice bearing B16 murine melanoma cells with inhibition rates of 67 and 61% at 100 and 30 mg/kg/day, respectively.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Oxazoles/chemistry , Oxazoles/pharmacology , Animals , Biochemistry/methods , Drug Design , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Melanoma/drug therapy , Mice , Mice, Inbred Strains , Tumor Cells, CulturedABSTRACT
2- or 6-(1-hydroxyiminoalkyl)-5,8-dimethoxy-1, 4-naphthoquinone(2- or 6-hyim-DMNQ) derived from the roots of Lithospermum erythrorhizon was synthesized for the evaluation of antitumor activities. Among those derivatives, 2-hyim-DMNQ-S33 was found to be a potent anticancer agent. This compound suppressed the proliferation of Radiation Induced Fibrosarcoma (RIF) cells in a dose-dependent manner. 2-hyim-DMNQ-S33 significantly prolonged the survival time by 239% as compared with Sarcoma 180 tumor-bearing control mice in vivo. We found that the compound significantly suppressed phosphorylation of extracellular signal-regulated kinase (pERK) and activated c-jun-N-terminal kinase (JNK) and protein kinase C (PKC)-alpha following 4 h-treatment. These findings indicate that 2-hyim-DMSQ-S33 exerts antitumor activities by regulating pERK, JNK and PKC-alpha.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Animals , Cell Division/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mitogen-Activated Protein Kinases/metabolism , Naphthoquinones/pharmacology , Neoplasms, Experimental/drug therapy , Protein Kinase C/metabolismABSTRACT
Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1-hydroxyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1-Hydroxyiminoalkyl)-DMNQ derivatives expressed greater antitumor action than (1-hydroxyalkyl)- or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ derivatives expressed higher antitumor action than 2-sudstituted ones, suggestive of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl group of butyl to octyl moiety showed T/C values of >400%.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Sarcoma 180/drug therapy , Animals , Indicators and Reagents , Injections, Intraperitoneal , Male , Mice , Mice, Inbred ICR , Neoplasm Transplantation , Structure-Activity Relationship , Survival AnalysisABSTRACT
Novel twelve esters of chlorambucil with 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone were synthesized and tested for their antitumor activity in mice bearing S-180 ascitic cells as well as cytotoxic activity against L1210 cells. Eight of them were highly cytotoxic on L1210 cells (ED(50), <6 microg mL(-1)) and derivatives 1 and 12 (T/C, 200 and 205%) appeared more active in vivo than chlorambucil (T/C, 168%).
Subject(s)
Anthraquinones/chemistry , Anthraquinones/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chlorambucil/chemistry , Animals , Chlorambucil/pharmacology , Drug Screening Assays, Antitumor , Leukemia L1210 , Male , Mice , Mice, Inbred ICR , Sarcoma, Experimental/drug therapy , Sarcoma, Experimental/mortality , Structure-Activity RelationshipABSTRACT
A series of 3-aryl-2-propenoates including cinnamates, (E)-methyl/ethyl 3-[2-(1,4-dimethoxy-5,8-dione)naphthalenyl]-2-propenoates (8ba, 8bb) and (E)-methyl/ethyl 3-[2-(1,4-dihydroxy-9,10-dione)anthracenyl]-2-propenoates (9aa,9ab) was synthesized and evaluated for antitumor cytotoxicity. It was found that the ortho- or para-dihydroxy funtionality on the aryl ring was essential for the cytotoxicity of cinnamates. Compounds 8ba, 8bb and 9aa, 9ab showed potent cytotoxicity against various tumor cell lines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Propane/analogs & derivatives , Propane/chemistry , Propane/pharmacology , Antineoplastic Agents/pharmacology , Caffeic Acids/chemistry , Cell Survival/drug effects , Cinnamates/chemistry , Humans , Tumor Cells, CulturedABSTRACT
Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1-hydroxyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1-Hydroxyiminoalkyl)-DMNQ derivatives expressed greater antitumor action than (1-hydroxyalkyl)- or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ derivatives expressed higher antitumor action than 2-sudstituted ones, suggestive of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl group of butyl to octyl moiety showed T/C values of >400%
Subject(s)
Antineoplastic Agents/therapeutic use , Naphthoquinones/therapeutic use , Sarcoma 180/drug therapy , Animals , Antineoplastic Agents/chemistry , Drug Screening Assays, Antitumor , Male , Mice , Mice, Inbred ICR , Naphthoquinones/chemistry , Tumor Cells, CulturedABSTRACT
6-(1-Acyloxyalkyl)-5,8-dimethoxy-1,4-naphthoquinone (DMNQ; 5,8-dimethoxy-1,4-naphthoquinone) derivatives were synthesized and examined for their inhibitory effect on DNA topoisomerase-I (Topo I) and their antiproliferative activity against L1210 cells. The Topo-I inhibitory effect of 6-(1-hydroxyalkyl)-DMNQ derivatives was found to be dependent on the size of the alkyl chains, suggesting that lipophilicity might be one important factor influencing the inhibitory effect. It was found that acylation of 6-(1-hydroxyalkyl)-DMNQ derivatives possessing alkyl chains of C2-C5 enhanced both bioactivities, suggesting that an increase of electrophilicity in the quinoid moiety makes the electrophilic arylation of bionucleophiles more favorable. It is noteworthy that 6-(1-heptanoyloxyethyl)-DMNQ exhibited both the most potent Topo I inhibitory activity (IC50, 11.5 microM) and the greatest antiproliferative activity (ED50, 0.05 microM) upon L1210 cells.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Topoisomerase I Inhibitors , Animals , Cell Division/drug effects , Leukemia L1210/drug therapy , Leukemia L1210/pathology , Structure-Activity RelationshipABSTRACT
All of 13 (E)-6-(1-alkyloxyiminomethyl)-5,8-dimethoxy-1,4-naphthoquinone derivatives synthesized showed high ED50 values, ranging from 0.1 to 0.3 microg/mL against L1210 cells. However, they were inactive on A549 cells. Nine compounds exhibited higher T/C (%) values (318-388%) than Adriamycin (T/C, 315%).
Subject(s)
Antineoplastic Agents/chemical synthesis , Leukemia L1210/drug therapy , Naphthoquinones/chemical synthesis , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/toxicity , Cell Survival/drug effects , Drug Design , Humans , Mice , Mice, Inbred ICR , Molecular Structure , Naphthoquinones/chemistry , Naphthoquinones/therapeutic use , Naphthoquinones/toxicity , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
A series of 2-(1-hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones (oximes) was synthesized and evaluated for cytotoxicity against L1210 cells and A549 cells. These oximes showed a greater cytotoxic activity compared to those of 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones as the hydroxyalkyl bioisosteres. The enhanced cytotoxicity assumed to be due to the improved water solubility of the hydroxyimino group. Moreover, it was found that the cytotoxicity of the oximes decreased with elongation of alkyl groups at the side chain. All of the synthesized compounds showed higher cytotoxicity against L1210 cells than A549 cells.
Subject(s)
Anthraquinones/chemical synthesis , Antineoplastic Agents/chemical synthesis , Animals , Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Humans , Leukemia L1210/drug therapy , Leukemia L1210/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
2-(1-Hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones were demethylated to produce 2-(1-hydroxyiminoalkyl)-1,4-dihydroxy-9,10-anthraquinones (1,4-dihydroxy-9,10-anthraquinone, DHAQ), oxime hydroxyl groups were in turn acylated to give the corresponding 2-(1-acyloxyiminoalkyl)-DHAQ derivatives. The anti-proliferative activity of 2-(1-hydroxyiminoalkyl)-DHAQ derivatives was found to be dependent on the size of an alkyl chain. Thus, DHAQ analogues with alkyl chains longer than heptyl had negligible anti-proliferative activity, whilst those compounds possessing shorter chains demonstrated moderate anti-proliferative activity (ED50, 2.73-19.21 microM). However, the antitumor activity as expressed by T/C values did not correlate with the anti-proliferative activity; 2-(1-hydroxyiminononyl)-DHAQ with an ED50 value of more than 20 microM exhibited potent antitumor activity (T/C, 166%). Only four of the 2-(1-hydroxyiminoalkyl)-DHAQ analogues showed good antitumor activity (T/C, > 150%); 2-(1-hydroxyiminobutyl)-DHAQ (T/C, 163%), 2-(1-hydroxyiminopentyl)-DHAQ (T/C, 180%) and 2-(1-hydroxyiminononyl)-DHAQ (T/C, 166%). Acylation of the hydroxyl group of these oximes enhanced the anti-proliferative activity and antitumor effects; 2-(1-propanoyloxyiminopropyl)-DHAQ (ED50, 4.41 microM; T/C, 221%) vs. 2-(1-hydroxyiminopropyl)-DHAQ (ED50, 14.64 microM; T/C, 100%) and 2-(1-propanoyloxyiminobutyl)-DHAQ (ED50, 2.65 microM; T/C, 202%) vs. 2-(1-hydroxyiminobutyl)-DHAQ (ED50, 16.43 microM; T/C, 163%).
Subject(s)
Anthraquinones/chemical synthesis , Antineoplastic Agents/chemical synthesis , Animals , Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Leukemia L1210/drug therapy , Leukemia L1210/pathology , Mice , Mice, Inbred ICR , Sarcoma 180/drug therapyABSTRACT
2- or 6-(1-Hydroxyiminoalkyl)-5,8-dimethoxy-1,4-naphthoquin-one (DMNQ) and 6-(1-propyloxyimino- alkyl)-DMNQ derivatives were synthesized, and their inhibitory effects on DNA topoisomerase-I (TOPO-I) and antiproliferative activities against L1210 cells were examined. In a comparison, it was found that 6-(1-hydroxyiminoalkyl)-DMNQ derivatives exhibited higher potencies in both bioactivities than 2-(1-hydroxyiminoalkyl)-DMNQ analogues, suggesting that the difference in bioactivities between two positional isomers might be due to the steric hindrance of the side chain. It is noteworthy that the optimal size of alkyl group for both bioactivities of 6-(1-hydroxyiminoalkyl)-DMNQ derivatives was pentyl to octyl (IC50, 22-29 microM) for the inhibition of TOPO-I and propyl to nonyl (ED50, 0.12-0.19 microM) for the antiproliferative activity. In addition, a similar potency of bioactivities was expressed by 6-(1-propyloxyiminoalkyl)-DMNQ derivatives, propylation products of the oximes.
Subject(s)
Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Inhibitory Concentration 50 , Leukemia L1210 , Mice , Naphthoquinones/chemical synthesis , Structure-Activity Relationship , Topoisomerase I Inhibitors , Tumor Cells, Cultured/drug effectsABSTRACT
Some 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives were synthesized and evaluated for inhibition of DNA topoisomerase I and cytotoxicity against L1210 cells. Compared with 2-acyl-DMNQ derivatives, 6-acyl-DMNQ compounds, bearing a higher electrophilic quinone moiety, showed a higher potency in the inhibition of DNA topoisomerase I and the cytotoxicity, implying the possible participation of electrophilic arylation in their bioactivities. Time and temperature dependence of the enzyme inhibition suggests that the arylation occurs irreversibly. Among the 6-acyl-DMNQ derivatives, the ones possessing an acyl group of an intermediate size (C(5)-C(9)) showed higher potency in their bioactivities than other derivatives. Furthermore, for the effective inhibition of DNA topoisomerase I, the size of acyl moiety of 6-acylated derivatives seems to be limited to < 12 carbon atoms.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Topoisomerase I Inhibitors , Animals , In Vitro Techniques , Leukemia L1210/drug therapy , Mice , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Oxidation-Reduction , Oxygen Consumption/drug effects , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone) was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusion on 2-isomers was greater than on 6-substituted ones, suggesting that S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.
Subject(s)
Antineoplastic Agents/metabolism , Glutathione Transferase/metabolism , Glutathione/metabolism , Liver/metabolism , Microsomes, Liver/metabolism , Naphthoquinones/metabolism , Animals , Mice , Naphthoquinones/pharmacology , Perfusion , Rats , Structure-Activity RelationshipABSTRACT
6-(1-azidoalkyl)-DMNQ derivatives compared to 2-(1-azidoalkyl)-DMNQ isomers, exhibited higher cytotoxic activity against L1210 mouse leukemia cells and stronger inhibition of DNA topoisomerase-I (TOPO-I), suggesting involvement of steric hindrance. However, similar antitumor activity against mice bearing S-180 cell was shown by 2- and 6-(1-azidoalkyl)-DMNQ derivatives.
Subject(s)
Antineoplastic Agents/chemical synthesis , Azides/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Naphthoquinones/chemical synthesis , Topoisomerase I Inhibitors , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Azides/chemistry , Azides/pharmacology , Chromatography, Thin Layer , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Leukemia L1210/pathology , Male , Mice , Mice, Inbred ICR , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Neoplasm Transplantation , Sarcoma, Experimental/drug therapy , Sarcoma, Experimental/pathology , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DMNQ) were synthesized and their structure was determined. The yield of GSH conjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of alkyl side chain influenced the chemical shift of quinonoid protons; the quinonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl, 6.51-6.59 ppm vs. other ones with R=butyl to heptyl, 6.64-6.68 ppm. This was explained to be due to a folding effect of longer alkyl group. Glutathione (GSH) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathionyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then, the adduct was autooxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DMNQ derivatives to their hydrogenated products. It was suggested that such an organic reaction might play an important role for a study of metabolism or toxicity of DMNQ derivatives in the living cells.
Subject(s)
Glutathione/chemical synthesis , Glutathione/metabolism , Naphthoquinones/chemical synthesis , Chromatography, Thin Layer , Drug Design , Glutathione/analogs & derivatives , Glutathione/chemistry , Hydrogen Peroxide/analysis , Indicators and Reagents , Naphthoquinones/chemistry , Oxidation-ReductionABSTRACT
6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones, expressing a higher reactivity in conjugation with glutathione, showed a greater potency in the inhibition of DNA topoisomerase-I and the cytotoxicity against L1210 cells than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying the participation of electrophilic arylation in the bioactivities. In further study 6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones with an alkyl group of shorter chain length (C2-C6) exerted a greater bioactivities than those with longer chain length(>C6).
Subject(s)
Antineoplastic Agents/chemistry , Enzyme Inhibitors/chemistry , Glutathione/chemistry , Leukemia L1210/pathology , Naphthoquinones/chemistry , Topoisomerase I Inhibitors , Animals , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Naphthoquinones/pharmacology , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Some analogues of Ginseng diyne were synthesized and tested for antiproliferative activity against L1210 cells. The epoxy moiety of panaxydol, isolated from the root of Panax ginseng, proved to be in the cis-form on comparison with synthetic specimens. Analysis of structure-activity relationship revealed that the presence of the heptadec-1-ene-4,6-diyn-3-ol moiety in the structure of the analogues was essential for their antiproliferative activity and that the epoxy and alkyl groups in the structure contributed to enhancement of the antiproliferative activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Leukemia L1210/drug therapy , Panax/therapeutic use , Phytotherapy , Plants, Medicinal , Animals , Antineoplastic Agents/therapeutic use , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).
Subject(s)
Anthracenes/chemical synthesis , Anthracenes/pharmacology , Anthraquinones/chemical synthesis , Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Thirty six 5,8-dimethoxy-1,4-naphthoquinone derivatives, which bear unsaturated alkyl side chain with ester bond, were synthesized and tested cytotoxic activity on L1210 cells and antitumor activity against ICR mice bearing S-180 cells. It could be recognized that the cytotoxicities of naphthoquinones with R1 being methyl and propyl (IV1-24) were not enhanced by replacing the alkanoyls with alkenoyls. In contrast, the introduction of the alkenoyl moieties on the compounds with R1 = hexyl (IV25-36) resulted in the enhancement of their cytotoxicities. Replacement of alkanoyl group with an alkenoyl group generally increased the T/C value of the mice bearing S-180 cells.
Subject(s)
Antineoplastic Agents , Antineoplastic Agents/pharmacology , Naphthoquinones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Drug Evaluation , In Vitro Techniques , Leukemia L1210/drug therapy , Mice , Mice, Inbred ICR , Naphthoquinones/chemical synthesis , Sarcoma 180/drug therapy , Tumor Cells, CulturedABSTRACT
Anti-cell adhesive activity and hemolytic action of herbal drugs were investigated. Among 232 herbal drugs tested, six showed a remarkable anti-cell adhesive activity, and the extract from the roots of Bupleurum falcatum (Umbelliferae), the semen of Psorala corylifolia (Leguminosae), and the semen of Areca catechu (Palmae) showed an anti-cell adhesive action at non-cytotoxic concentrations. Saikosaponins-a, d and e, isolated from the roots of Bupleurum falcatum, exhibited a potent anti-cell adhesive activity and a strong hemolytic action. In a structure-activity relationship for both activities, it seems that a sugar moiety and an ether linkage between C-13 and C-28 are required for good bioactivities. In addition, saikosaponin d with a beta-hydroxy group at C-16 was more potent than saikosaponin a possessing an alpha-hydroxy group. Taken together, it is suggested that the mechanism for anti-cell adhesive activity of saikosaponin may resemble that for their hemolytic action.