Total Syntheses and Cytotoxic Evaluations of Cryptolactones A1, A2, B1, B2, and Their Derivatives.

The cryptolactones A1, A2, B1, and B2 isolated from a Cryptomyzus sp. aphid were synthesized via the Mukaiyama aldol reaction and olefin metathesis. Their antipodes and derivatives were also synthesized by the same strategy to investigate structure-activity relationships. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 2.1-42 µM.

Isolation and total syntheses of cytotoxic cryptolactones A1, A2, B1, and B2: α,ß-unsaturated δ-lactones from a Cryptomyzus sp. aphid.

The cryptolactones A1, A2, B1, and B2, which are α,ß-unsaturated δ-lactones, were isolated from a Cryptomyzus sp. aphid. The structures were established by 1-D and 2-D NMR spectra and CI-HRMS. Their absolute configurations were determined with the Kusumi-Mosher method, combined with asymmetric total syntheses. The syntheses were accomplished with the Mukaiyama aldol reaction and olefin metathesis, which utilized the second-generation Grubbs catalyst for the key steps. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 0.97-5.3 µM.

Viridaphin A1 glucoside, a green pigment possessing cytotoxic and antibacterial activity from the aphid Megoura crassicauda.

A green pigment, viridaphin A1 glucoside (1), was isolated from the green aphid Megoura crassicauda. One- and two-dimensional NMR spectrometric analyses of 1 and its aglycone established the structure as an octacyclic compound. Viridaphin A1 glucoside exhibited cytotoxicity against HL-60 human tumor cells with an IC50 of 23 µM and antibacterial activity against Bacillus subtilis NBRC 3134 with a minimum inhibitory concentration of 10.0 µg/mL. These results suggested that aphid pigments may protect aphids from invasive species, including viruses and bacteria.

A role of uroleuconaphins, polyketide red pigments in aphid, as a chemopreventor in the host defense system against infection with entomopathogenic fungi.

Four red polyketide pigments, uroleuconaphins A1 (1) and B1 (2) and their glucosides 3 and 4, were isolated from the red goldenrod aphid Uroleucon nigrotuberculatum. Although these red pigments exist only as glucosides 3 and 4 in the intact insect body, 3 and 4 convert instantly to aglycones 1 and 2 at death. Pigments 1 and 2 inhibited the growth of Lecanicillium sp. (Ascomycota: Cordycipitaceae) and 1, 2, and 3 were active against Conidiobolus obscurus (Entomophthoromycota; Entomophthorales); these fungal species are pathogenic. We therefore regard aphid pigments 1-4 as chemopreventive agents that aid in the resistance of infection by entomopathogenic fungi at the level of the individual aphid and/or at the species level.

A practical total synthesis of (+)-antimycin A9.

(+)-Antimycin A9 (AA9) isolated from a cultured broth of Streptomyces sp. K01-0031 was synthesized via an asymmetric aldol reaction using Oppolzer's sultam as a chiral auxiliary.

Symbiotic bacterium modifies aphid body color.

Color variation within populations of the pea aphid influences relative susceptibility to predators and parasites. We have discovered that infection with a facultative endosymbiont of the genus Rickettsiella changes the insects' body color from red to green in natural populations. Approximately 8% of pea aphids collected in Western Europe carried the Rickettsiella infection. The infection increased amounts of blue-green polycyclic quinones, whereas it had less of an effect on yellow-red carotenoid pigments. The effect of the endosymbiont on body color is expected to influence prey-predator interactions, as well as interactions with other endosymbionts.

Pigments from Uroleucon nigrotuberculatum induce apoptosis in HL60 human leukemia cells, implicating intracellular oxidative stress and activation of caspases.

Two pigmented compounds from Uroleucon nigrotuberculatum, uroleuconaphin-B(1) [corrected] (H427) and uroleuconaphin-A(1) [corrected] (H373), significantly diminished the cell viability of HL60 cells with IC50 of 10 microM and 30 microM, respectively, in an 18 h-dye uptake assay. Both H427 and H373 augmented the levels of intracellular reactive oxygen species (ROS) and induced apoptosis as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. ROS augmentation by both H427 and H373 was inhibited by N-acetylcysteine (NAC) and alpha-tocopherol. The apoptosis induced by H427 was inhibited efficiently with NAC and caspase-8 inhibitor but less efficiently with alpha-tocopherol and caspase-9 inhibitor. These findings suggested that these pigments have pro-apoptotic activities via oxidative stress.