The Effect of Summer Harvesting of Phragmites australis on Growth Characteristics and Rhizome Resource Storage

The effect of harvesting the aboveground biomass on the growth of Phragmites australis in the subsequent growing season was investigated following cutting in June or July. Seasonal changes in rhizome biomass and total nonstructural carbohydrate (TNC) in seven age categories, from newly formed to six-years-old, were monitored for the two treatment stands and a control stand. The growth of the stands, as indicated by the aboveground biomass, showed a significant decline due to cutting in June but did not show a significant difference due to cutting in July, compared to that of the control stand. The timing of harvesting of aboveground biomass affected the annual rhizome resource allocation. A similar trend was observed for the pattern of resource allocation, as described by biomass variation of different rhizome-age categories for July-cut and control stands. However, the biomass of June-harvested rhizome categories tended to be smaller than the other two stands, indicating substantially reduced resource storage as a direct result of harvesting the aboveground biomass during the previous growing season. This implies that cutting of aboveground biomass in June is a better option for control of P. australis stands than cutting later in summer.     

Bidesmosidic saponins from the fruits of Diploclisia glaucescens

Chemical investigation of methanol extract of the fruits of Diploclisia glaucescens (Menispermaceae) furnished two new bidesmosidic saponins 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]phytolaccagenic acid 28-O-beta-D-glucopyranosyl ester, 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]phytolaccagenic acid 28-O-beta-D-glucopyranosyl ester, together with known 3-O-beta-D-glucopyranosylphytolaccagenic acid 28-O-beta-D-glucopyranosyl ester and 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]serjanic acid 28-O-beta-D-glucopyranosyl ester. The last saponin is reported for the first time from the family Menispermaceae.     

3-Deoxy-1beta,20-dihydroxyecdysone from the leaves of Diploclisia glaucescens

Chemical investigation of methanol extract of the leaves of Diploclisia glaucescens of the family Menispermaceae furnished a new ecdysteroid, 3-deoxy-1beta,20-dihydroxyecdysone. The structure of the new ecdysteroid was established on detailed analysis of spectral data. The 3-deoxy ecdysteroid showed 40% potency of 20-hydroxyecdysone in the spiracle index assay using the fourth instar larvae of the silkworm Bombyx mori.     

Construction and functionalization of pyranone ring fused with pyran moiety: Design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins

Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1). Elegant synthesis of these compounds was performed via a multi-step sequence consisting of MCR, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C–C bond forming reactions. The overall strategy involved the construction of a pyran ring followed by the fused pyranone moiety and subsequent functionalization at C-8 position of the resultant core pyrano[4,3-b]pyran-5(4H)-one framework. The crystal structure analysis of a representative iodolactonized product (6d) is presented. Some of the synthesized compounds showed promising inhibitory activities when tested against yeast sir2 in vitro. The compound 6g showed dose dependent inhibition (IC₅₀ = 78.05 μM) of yeast sir2 and good interactions with this protein in silico.     

Geranylated phenolic constituents from the fruits of Artocarpus nobilis

Chemical investigation of the combined dichloromethane and ethyl acetate extracts of the fruits of Artocarpus nobilis, furnished four new geranylated phenolic constituents, 2,4,4'-trihydroxy-3-[(2E)-5-methoxy-3,7-dimethylocta-2,6-dienyl]chalcone (4), 1-(3,4-dihydro-3,5-dihydroxy-2-methyl-2-(3-methyl-2-butenyl)-2H-1-benzopyran-6-yl-3-(4-hydroxyphenyl)-2(E)-propen-1-one (5), 8-geranyl-3',4',7-trihydroxyflavone (8), 3'-geranyl-4',5,7-trihydroxyflavanone (9), together with known related compounds, xanthoangelol (1), xanthoangelol B (2), 3-geranyl-2,3',4,4'-tetrahydroxychalcone (3), lespeol (6), 8-geranyl-4',7-dihydroxyflavanone (7), and isonymphaeol-B (10). Compounds 3, 8 and 10 showed strong antioxidant activity against DPPH radical by spectrophotometric method.     

Cooperative damage recognition by UvrA and UvrB: identification of UvrA residues that mediate DNA binding

Nucleotide excision repair (NER) is responsible for the recognition and removal of numerous structurally unrelated DNA lesions. In prokaryotes, the proteins UvrA, UvrB and UvrC orchestrate the recognition and excision of aberrant lesions from DNA. Despite the progress we have made in understanding the NER pathway, it remains unclear how the UvrA dimer interacts with DNA to facilitate DNA damage recognition. The purpose of this study was to define amino acid residues in UvrA that provide binding energy to DNA. Based on conservation among approximately 300 UvrA sequences and 3D-modeling, two positively charged residues, Lys680 and Arg691, were predicted to be important for DNA binding. Mutagenesis and biochemical analysis of Bacillus caldontenax UvrA variant proteins containing site directed mutations at these residues demonstrate that Lys680 and Arg691 make a significant contribution toward the DNA binding affinity of UvrA. Replacing these side chains with alanine or negatively charged residues decreased UvrA binding 3-37-fold. Survival studies indicated that these mutant proteins complemented a WP2 uvrA(-) strain of bacteria 10-100% of WT UvrA levels. Further analysis by DNase I footprinting of the double UvrA mutant revealed that the UvrA DNA binding defects caused a slower rate of transfer of DNA to UvrB. Consequently, the mutants initiated the oligonucleotide incision assay nearly as well as WT UvrA thus explaining the observed mild phenotype in the survival assay. Based on our findings we propose a model of how UvrA binds to DNA.     

Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles

Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.     

Stalosylglobotetraosylceramide: A marker for amyotropic lateral sclerosis

Gangliosides of healthy and pathologic muscles (amyotropic lateral sclerosis and facio-scapulo-humeral muscular dystrophy) were studied. Total ganglioside content of the affected muscles was approximately 2 fold higher than the unaffected muscles. Our results showed that ALS muscle contained a ganglioside which was absent in the unaffected and FSH muscular dystrophic muscles. Based on the results of hydrolysis with $\text{Vibrio cholerae}$ neuraminidase and subsequent reactivity of the asialo derivative towards anti-globotetraosylceramide, we propose that the ALS ganglioside is sialosylglobtetraosylceramide, NeuAc(α2–3)GalNAc(β1–3)Gal(α1–4)Gal(β1–4)Glc-Cer.     

Phosphorus concentration in sediment, water and tissues of␣three submerged macrophytes of Myall Lake, Australia

Phosphorus content in sediment, water and tissues of three macrophyte species growing in Myall Lake, Australia were studied from January to November, 2004. The sites investigated were North–West (NW), North–East (NE), South–West (SW) bays and Central deep area of the lake (CL). The objective of this study was to investigate how total phosphorus (TP) in plant tissues relate to phosphorus pools and the role played by the aquatic macrophyte species under investigation in phosphorus recycling in the lake. Of the four investigated sites of the lake, TP in plant tissues were significantly higher in North–West and South–West bays compared to the rest. Najas marina had significantly higher TP content (e.g., 1.55 and 1.44 mg/g dw.; P < 0.05) for NW and SW respectively, than the other two species. N. marina is a rooted macrophyte while charophytes (C. fibrosa and Nitella hyalina) are pseudo-rooted macrophytes. Total phosphorus in the sediment and water column were significantly higher in Central deep area of the lake compared to the other three bays (P < 0.05, n 5). Soluble reactive phosphorus (SRP) and total dissolved phosphorus (TDP) in sediment pore water correlated significantly with phosphorus content in the tissue of N. marina ( ; ) as well as TP in sediment (␣ and ). Using the two-compartmental uptake model, it was observed that, sediment was the main compartment through which Ni. hyalina obtained phosphorus while for the other two species, water column was the uptake route for the phosphorus. These correlations suggest that, water column and sediments are important pathways for phosphorus uptake in plants.