Effect of the structure of dietary epoxylignan on its cytotoxic activity: relationship between the structure and the activity of 7,7′-epoxylignan and the introduction of apoptosis by caspase 3/7

<p>We compared the cytotoxic activities of dietary epoxylignans and their stereoisomers and found (−)-verrucosin, which is (7<i>S</i>,7′<i>R</i>,8<i>R</i>,8′<i>R</i>)-7,7′-epoxylignan, to be the most cytotoxic epoxylignan against HeLa cells (IC₅₀ = 6.6 μM). On the other hand, the activity was about a factor of 10 less against HL-60. In this research on the relationship between the structure and cytotoxic activity of (−)-verrucosin <b>13</b>, the 7-(4-methoxyphenyl)-7′-(3,4-dimethoxyphenyl) derivative <b>60</b>, for which the activity (IC₅₀ = 2.4 μM) is three times greater than (−)-verrucosin <b>13,</b> was discovered. The induction of apoptosis by caspase 3/7 was observed upon treatment with the (−)-verrucosin derivative.</p> <p>3′,4,4′-Trimethoxy-7,7′-epoxylignan showed highest IC₅₀ value (2.4 μM) in this structure–cytotoxic activity relationship experiment of 7,7′-epoxylignan. The IC₅₀ value of natural (−)-verrucosin was 6.6 μM.</p

Cytotoxic Activity of Dietary Lignan and Its Derivatives: Structure–Cytotoxic Activity Relationship of Dihydroguaiaretic Acid

Cytotoxic activities of synthesized lignan derivatives were estimated by WST-8 reduction assay against HL-60 and HeLa cells to show the structure–activity relationship. The activities of some effective compounds were examined against Colon 26 and Vero cells. Dietary secoisolariciresinol (SECO, <b>1</b>) and its metabolite, 9,9′-anhydro­secoiso­lariciresinol (<b>2</b>), did not show the cytotoxic activity. On the other hand, all stereoisomers of dihydroguaiaretic acid (DGA, 9,9′-dehydroxy­secoiso­lariciresinol, <b>3</b>–<b>5</b>) exhibited the activity (IC₅₀: around 30 μM). The IC₅₀ value of (8<i>R</i>,8′<i>R</i>)-9-butyl DGA derivative <b>13</b> was around 6 μM. This fact means that the hydrophobic group was advantageous for higher activity at 9- and 9′-positions. By the evaluation of the effect of 7and 7′-aryl group on the activity, we discovered the highest activity of (8<i>R</i>,8′<i>R</i>)-7-(3-hydroxy-4-methoxyphenyl)-7′-(2-ethoxyphenyl) DGA derivative <b>47</b> showing around 1 μM of IC₅₀ value, which is about 24-fold higher activity than that of natural (8<i>R</i>,8′<i>R</i>)-DGA. The derivative of dietary lignan showed the high cytotoxic activity

Acute Larvicidal Activity against Mosquitoes and Oxygen Consumption Inhibitory Activity of Dihydroguaiaretic Acid Derivatives

(−)-Dihydroguaiaretic acid (DGA) and its derivatives having 3-hydroxyphenyl (3-OH-DGA) and variously substituted phenyl groups instead of 3-hydroxy-4-methoxyphenyl groups were synthesized to measure their larvicidal activity against the mosquito <i>Culex pipiens</i> Linnaeus, 1758 (Diptera: Culicidae). Compared with DGA and 3-OH-DGA (LC₅₀ (M), 3.52 × 10^–5 and 4.57 × 10^–5, respectively), (8<i>R</i>,8′<i>R</i>)-lignan-3-ol (<b>3</b>) and its 3-Me (<b>10</b>), 2-OH (<b>12</b>), 3-OH (<b>13</b>), and 2-OMe (<b>15</b>) derivatives showed low potency (ca. 6–8 × 10^–5 M). The 4-Me derivative (<b>11</b>) showed the lowest potency (12.1 × 10^–5 M), and the 2-F derivative (<b>4</b>) showed the highest (2.01 × 10^–5 M). All of the synthesized compounds induced an acute toxic symptom against mosquito larvae, with potency varying with the type and position of the substituents. The 4-F derivative (<b>6</b>), which killed larvae almost completely within 45 min, suppressed the O₂ consumption of the mitochondrial fraction, demonstrating that this compound inhibited mitochondrial O₂ consumption contributing to a respiratory inhibitory activity

Enzyme-Linked Immunosorbent Assay with Monoclonal and Single-Chain Variable Fragment Antibodies Selective to Coplanar Polychlorinated Biphenyls

Coplanar polychlorinated biphenyls (Co-PCBs) consisting of non-<i>ortho</i> and mono-<i>ortho</i>-chlorinated PCBs are dioxin-like compounds and cause wide contamination in the environment. To monitor Co-PCB residues, it was attempted to establish an enzyme-linked immunosorbent assay (ELISA) with monoclonal and recombinant antibodies selective to Co-PCBs. When 3,3′,5,5′-tetrachlorobiphenoxybutyric acid (PCBH)–keyhole limpet hemocyanin conjugate was immunized into mice, two monoclonal antibodies, Mab-0217 and Mab-4444, were obtained. 3,3′,5,5′-Tetrachlorobiphenyl (PCB80) was determined with an IC₅₀ value of 2.6 and 0.46 ng mL^–1 in ELISA based on Mab-0217 and Mab-4444, respectively. Mab-4444 cross-reacted with Co-PCB congeners, except for PCB77 and PCB81. Mab-0217 reacted with PCB80 and cross-reacted with PCB111. A single-chain variable fragment (scFv) antibody derived from Mab-4444 was produced in recombinant Escherichia coli cells. The scFv antibody showed nearly the same sensitivity toward PCBH as the parent monoclonal antibody in ELISA. These results clearly suggested that Mab-4444 and its scFv antibodies were suitable for monitoring the representative congeners of Co-PCBs

Revised Stereochemistry of Ficifolidione and Its Biological Activities against Insects and Cells

Ficifolidione (<b>1</b>), a moderately active insecticidal compound from two species of <i>Myrtaceae</i>, and its derivatives were synthesized to evaluate their insecticidal activity. X-ray crystallographic analyses and specific rotation values of ficifolidione and its C-4 (<b>2</b>) demonstrated that the structure of ficifolidione differs from the reported absolute structure; that is, the C-4 configuration of ficifolidione should have an <i>S</i> configuration. The reported insecticidal activity of ficifolidione (<b>1</b>) and its C-4 epimer (<b>2</b>) against adult houseflies (<i>Musca domestica</i>), mosquito larvae (<i>Culex pipiens</i>), and cutworms (<i>Spodoptera litura</i>) was not observed. The cytotoxicities of ficifolidione and its derivatives (<b>1</b>–<b>4</b>) against four cell lines, Sf9, Colon26, HL60, and Vero, were also measured because ficifolidione has a phloroglucinol-derived moiety, a motif that is often present in the structure of cytotoxic chemicals. Compound <b>1</b> exhibited IC₅₀ values of ca. 32, 9, 3, and 12 μM for Sf9, Colon26, HL60, and Vero cells, respectively, indicating that ficifolidione possesses selective cytotoxicity against the four cell lines. In HL60 cells treated with <b>1</b>, DNA fragmentation and the activation of procaspase 3 were observed, suggesting that the cytotoxicity is induced by apoptosis

Revised Stereochemistry of Ficifolidione and Its Biological Activities against Insects and Cells

Ficifolidione (<b>1</b>), a moderately active insecticidal compound from two species of <i>Myrtaceae</i>, and its derivatives were synthesized to evaluate their insecticidal activity. X-ray crystallographic analyses and specific rotation values of ficifolidione and its C-4 (<b>2</b>) demonstrated that the structure of ficifolidione differs from the reported absolute structure; that is, the C-4 configuration of ficifolidione should have an <i>S</i> configuration. The reported insecticidal activity of ficifolidione (<b>1</b>) and its C-4 epimer (<b>2</b>) against adult houseflies (<i>Musca domestica</i>), mosquito larvae (<i>Culex pipiens</i>), and cutworms (<i>Spodoptera litura</i>) was not observed. The cytotoxicities of ficifolidione and its derivatives (<b>1</b>–<b>4</b>) against four cell lines, Sf9, Colon26, HL60, and Vero, were also measured because ficifolidione has a phloroglucinol-derived moiety, a motif that is often present in the structure of cytotoxic chemicals. Compound <b>1</b> exhibited IC₅₀ values of ca. 32, 9, 3, and 12 μM for Sf9, Colon26, HL60, and Vero cells, respectively, indicating that ficifolidione possesses selective cytotoxicity against the four cell lines. In HL60 cells treated with <b>1</b>, DNA fragmentation and the activation of procaspase 3 were observed, suggesting that the cytotoxicity is induced by apoptosis

Revised Stereochemistry of Ficifolidione and Its Biological Activities against Insects and Cells

Ficifolidione (<b>1</b>), a moderately active insecticidal compound from two species of <i>Myrtaceae</i>, and its derivatives were synthesized to evaluate their insecticidal activity. X-ray crystallographic analyses and specific rotation values of ficifolidione and its C-4 (<b>2</b>) demonstrated that the structure of ficifolidione differs from the reported absolute structure; that is, the C-4 configuration of ficifolidione should have an <i>S</i> configuration. The reported insecticidal activity of ficifolidione (<b>1</b>) and its C-4 epimer (<b>2</b>) against adult houseflies (<i>Musca domestica</i>), mosquito larvae (<i>Culex pipiens</i>), and cutworms (<i>Spodoptera litura</i>) was not observed. The cytotoxicities of ficifolidione and its derivatives (<b>1</b>–<b>4</b>) against four cell lines, Sf9, Colon26, HL60, and Vero, were also measured because ficifolidione has a phloroglucinol-derived moiety, a motif that is often present in the structure of cytotoxic chemicals. Compound <b>1</b> exhibited IC₅₀ values of ca. 32, 9, 3, and 12 μM for Sf9, Colon26, HL60, and Vero cells, respectively, indicating that ficifolidione possesses selective cytotoxicity against the four cell lines. In HL60 cells treated with <b>1</b>, DNA fragmentation and the activation of procaspase 3 were observed, suggesting that the cytotoxicity is induced by apoptosis