Total synthesis of heliannone A and (R,S)-heliannone B, two bioactive flavonoids from Helianthus annuus cultivars

The total synthesis of heliannone A (1) and (R,S)-heliannone B (2), two bioactive flavonoids originally isolated from Helianthus annuus cultivars, is described.     

A new biflavonoid from Ochna beddomei

A new biflavonoid, 2,3-dihydroochnaflavone 7,4',7'-tri-O-methyl ether (1) together with two known biflavonoids namely, 2,3-dihydroochnaflavone (2) and ochnaflavone (3) were isolated from the stem bark of Ochna beddomei. The structures were determined by means of spectral and chemical studies.     

New 2'-oxygenated flavonoids from Andrographis affinis

Three new 2'-oxygenated flavonoids, (2S)-5,7,2',3',4'-pentamethoxyflavanone (1), 5-hydroxy-7,8,2',5'-tetramethoxyflavone (2), and echioidinin 2'-O-beta-d-(6' '-O-acetyl) glucopyranoside (3), together with four known flavonoids, 7-O-methyldihydrowogonin, 7-O-methylwogonin, skullcapflavone I 2'-methyl ether, and skullcapflavone I, and two diterpenoids, andrograpanin and 14-deoxy-11,12-didehydroandrographolide, were isolated from the whole plant of Andrographis affinis. The structures were elucidated by spectral and chemical studies.     

Flavonol glycosides from cassia hirsuta

A new flavonol glycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-rhamnopyranoside (1), was isolated from the flowers of Cassia hirsuta along with two known flavonol glycosides, kaempferol 3-O-rutinoside and rutin. The structure of compound 1 has been established on the basis of spectral data and by acid hydrolysis.     

A New Naphthoquinone from Bombax Malabaricum

A new naphthoquinone 1 together with 7-hydroxycadalene (2) and 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (3) were isolated from the heartwood of Bombax malabaricum. The new naphthoquinone was characterized as 7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthoquinone (1) based on spectral and chemical studies.     

Detection of oxidative species and low-molecular-weight DNA in skin following dermal exposure with JP-8 jet fuel.

Dermal absorption of JP-8 jet fuel can lead to skin irritation within hours after exposure. This study detected the formation of oxidative species and low-molecular-weight DNA in rat skin as potential indicators of JP-8-induced skin injury. At 0, 1, 2, 4 and 6 h after the beginning of a 1-h exposure, skin samples were removed and analyzed for oxidative species formation and low-molecular-weight DNA analysis. At 1, 2 and 4 h, mean oxidative species levels increased significantly (P < 0.05) above unexposed samples. Significantly higher (P < 0.05) low-molecular-weight DNA values were observed at 4 and 6 h compared with unexposed controls. These results demonstrate significant increases in oxidative species and low-molecular-weight DNA levels in the skin following dermal exposure to JP-8. These responses may serve as indicators of skin injury following exposure to JP-8 jet fuel and other volatile chemicals or mixtures.     

Genomic landscape of liposarcoma

Liposarcoma (LPS) is the most common type of soft tissue sarcoma accounting for 20% of all adult sarcomas. Due to absence of clinically effective treatment options in inoperable situations and resistance to chemotherapeutics, a critical need exists to identify novel therapeutic targets. We analyzed LPS genomic landscape using SNP arrays, whole exome sequencing and targeted exome sequencing to uncover the genomic information for development of specific anti-cancer targets. SNP array analysis indicated known amplified genes (MDM2, CDK4, HMGA2) and important novel genes (UAP1, MIR557, LAMA4, CPM, IGF2, ERBB3, IGF1R). Carboxypeptidase M (CPM), recurrently amplified gene in well-differentiated/de-differentiated LPS was noted as a putative oncogene involved in the EGFR pathway. Notable deletions were found at chromosome 1p (RUNX3, ARID1A), chromosome 11q (ATM, CHEK1) and chromosome 13q14.2 (MIR15A, MIR16-1). Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%). Further, in vitro and in vivo functional studies provided evidence for the tumor suppressor role for Neurofibromin 1 (NF1) gene in different subtypes of LPS. Pathway analysis of recurrent mutations demonstrated signaling through MAPK, JAK-STAT, Wnt, ErbB, axon guidance, apoptosis, DNA damage repair and cell cycle pathways were involved in liposarcomagenesis. Interestingly, we also found mutational and copy number heterogeneity within a primary LPS tumor signifying the importance of multi-region sequencing for cancer-genome guided therapy. In summary, these findings provide insight into the genomic complexity of LPS and highlight potential druggable pathways for targeted therapeutic approach.