Synthesis of Phenoxazinone Derivatives and Antiproliferative Activities on Wild-type and Drug-resistant Tumor Cells

A series of novel phenoxazinone derivatives （1-6） were designed and synthesized for evaluating their antitumor activities. The antiproliferative activities of the prepared compounds against representative human neoplastic cell lines were evaluated by MTF assay. The results showed that most of them inhibited cell proliferation in a submicromolar to rnicromolar range. These compounds were also evaluated against KBv200 and MCF-7/Adr cell lines, which overexpress the MDR/P-glycoprotein drug efflux pump responsible for drug resistance, and had a more potential for resisting MDR than their lead compound APO.

Cloning and Characterization of karmoisin Homologue Gene(Nlka) in Two Brown Planthopper Strains with Different Eye Colors

The brown planthopper （BPH）, Nilaparvata lugens, is a destructive insect pest of rice throughout Asia. Different from brown-eye color wild type, BPH also has red-eye color mutation phenotype. As a visible genetic marker, the red-eye mutant in BPH is a valuable material. To reveal the eye color mutation mechanism, a karmoisin homologue gene （named as Nlka） was cloned from BPH. And karmoisin is always deemd as a xanthommatin-related gene in other insects, encoding phenoxazinone synthetase （PHS）. Nlka is consisted of 7 exons and encodes a protein with 502 amino acids （NIKA）. NIKA showed high amino acid identities with its insect homologues （48.8%-51.8%）. Nlka transcripts can be detected at all the developmental stages and in all tissues tested, including egg, nymph, adult, body wall, ovary, fat body, midgut and Malpighian tubule. However, no constant In/Del or non-synonymous mutation was observed between the mutant and the wild type strains. Quantitative real-time PCR experiment also showed that Nlka transcript level had no significant differences between them. These results indicated that Nlka is not the target gene causing the red-eye color mutation phenotype of BPH. Through the second structure and motif analysis, the present study also showed that all the proteins deduced from the karmoisin genes in insects may be members of monocarboxylate transporters （MCTs） rather than PHSs.

Synthesis of New Near-infrared Fluorescent Dyes

A new near-infrared fluorescent dye, 9-N-(2-hydroxyethyl)-N-methylamino-6-carbethoxy-5H-benzo[a]phenoxazin-5-one 1, was prepared from the reaction of N-(2-hydroxyethyl)-N-methyl-4-nitrosoaniline hydrochloride and ethyl 1,3-dihydroxynaphthoate. Five more fluorescent compounds were synthesized by the reaction of the resulting dye 1 with appropriate amino acid or carboxylic acids.

karmoisin and cardinal ortholog genes participate in the ommochrome synthesis of Nilaparvata lugens (Hemiptera:Delphacidae)

Ommochrome is the major source for eye coloration of all insect species so far examined.Phenoxazinone synthetase (PHS)has always been regarded as the terminal step enzyme for ommochrome formation,which is encoded by cardinal or karmoisin genes. Our previous study indicated that the karmoisin ortholog gene (Nl-karmoisin)product in the brown planthopper (BPH)was a monocarboxylate transporter,while not a PHS. Here,based on full-length complementary DNA,the cardinal ortholog gene in BPH (Nl-cardinal)product was predicted to be a haem peroxidase rather than a PHS.We suggest for the first time that neither karmoisin nor cardinal encodes the PHS,but whether PHS participates in BPH eye pigmentation needs further research.Nymphal RNA interference (RNAi)experiments showed that knockdown Nl-cardinal transcript led the BPH ocelli and compound eye to color change from brown to red,while knockdown Nl-karmoisin only made the ocelli present the red phenotype.Notably,not only the Nl-cardinal transcript, dscd injection (Nl-cardinal targeting double-stranded DNA (dsRNA))also significantly reduced the Nl-karmoisin transcript by 33.7%,while dska (Nl-karmoisin targeting dsRNA) injection did not significantly change the Nl-cardinal transcript.Considering the above RNAi and quantitative real-time polymerase chain reaction results,we propose that Nl-cardinal plays a more important role in ommochrome synthesis than Nl-karmoisin,and it may be an upstream gene of Nl-karmoisin.The present study suggested that both karmoisin and cardinal ortholog genes play a role in ommochrome synthesis in a hemimetabolous insect.