Carotenoid inhibitors reduce strigolactone production and Striga hermonthica infection in rice

The strigolactones are internal and rhizosphere signalling molecules in plants that are biosynthesised through carotenoid cleavage. They are secreted by host roots into the rhizosphere where they signal host-presence to the symbiotic arbuscular mycrorrhizal (AM) fungi and the parasitic plants of the Orobanche, Phelipanche and Striga genera. The seeds of these parasitic plants germinate after perceiving these signalling molecules. After attachment to the host root, the parasite negatively affects the host plant by withdrawing water, nutrients and assimilates through a direct connection with the host xylem. In many areas of the world these parasites are a threat to agriculture but so far very limited success has been achieved to minimize losses due to these parasitic weeds. Considering the carotenoid origin of the strigolactones, in the present study we investigated the possibilities to reduce strigolactone production in the roots of plants by blocking carotenoid biosynthesis using carotenoid inhibitors. Hereto the carotenoid inhibitors fluridone, norflurazon, clomazone and amitrole were applied to rice either through irrigation or through foliar spray. Irrigation application of all carotenoid inhibitors and spray application of amitrole significantly decreased strigolactone production, Striga hermonthica germination and Striga infection, also in concentrations too low to affect growth and development of the host plant. Hence, we demonstrate that the application of carotenoid inhibitors to plants can affect S. hermonthica germination and attachment indirectly by reducing the strigolactone concentration in the rhizosphere. This finding is useful for further studies on the relevance of the strigolactones in rhizosphere signalling. Since these inhibitors are available and accessible, they may represent an efficient technology for farmers, including poor subsistence farmers in the African continent, to control these harmful parasitic weeds.     

Synthesis and biological evaluation of novel oxindole-based RTK inhibitors as anti-cancer agents

Given that receptor tyrosine kinases (RTKs) have emerged as key regulators of all aspects of cancer development, including proliferation, invasion, angiogenesis and metastasis, the RTK family represents an important therapeutic target for anti-cancer drug development. Oxindole structure has been used in RTK inhibitors such as SU4984 and intedanib. In this study, two series of new heterocyclic compounds containing oxindole scaffold have been designed and synthesized, and their inhibitory activity against the proliferation of nine cancer cell lines has been evaluated. Among them, compounds 9a and 9b displayed the strongest anti-proliferative activity with the IC₅₀s below 10 μM. Flow cytometric analysis showed that the compounds 9a and 9b dose-dependently arrested the cell cycle at G0/G1 phase. Although the leading compounds SU4984 and intedanib targets FGFR1, the kinase activity test revealed that these compounds only showed slight inhibitory activity on FGFR1 kinase. Further enzymatic test aided by molecular docking simulation in the ATP-binding site demonstrated that 9a and 9b are potent inhibitors of c-Kit kinase. These compounds are worthy of further evaluation as anticancer agents.     

Fungal pathogens of Euphorbia heterophylla and E. hirta in Brazil and their potential as weed biocontrol agents

A two-year survey of the fungi associated with two important congeneric pantropical weeds, Euphorbia heterophylla and E. hirta, was conducted in part of their native range in southern Brazil. Sampling was concentrated mainly in Rio de Janeiro State and ten species were identified as pathogens of these weeds. Two taxa, Botrytis ricini and Uromyces euphorbiae, were common to both weed hosts. Alternaria euphorbiicola, Bipolaris euphorbiae, Melampsora sp., Oidium sp. and Sphaceloma poinsettiae were recorded only from E. heterophylla, whereas Colletotrichum gloeosporioides, Sphaceloma sp. and Sphaerotheca fuliginea were restricted to E. hirta. Botrytis ricini and Colletotrichum gloeosporioides are new records for E. hirta, and Alternaria euphorbiicola and Sphaerotheca fuliginea are new host records for Brazil. Bipolaris euphorbiae, previously identified as Helminthosporium sp., is considered to be the correct name for the causal agent of a major disease of E. heterophyllum in Brazil. The potential of these pathogens as biocontrol agents is discussed and the mycobiota associated with both these weeds worldwide is reviewed.This revised version was published online in October 2005 with corrections to the Cover Date.     

Insect herbivores associated with the introduced weed Bidens frondosa L. (Asteraceae) in Korea,and their potential role as augmentative biological control agents

The annual herb Bidens frondosa L., native to North America, is an invasive weed. Currently no information is available on the insect herbivores associated with this weed in Korea. A survey was carried out at two‐weekly intervals from May to October 2008 at two sites, and the incidence and abundance of various insect herbivores studied. A total nine species of insects was recorded and among them the defoliating caterpillar Hadjina chinensis (Wallengren) (Lepidoptera) was the only species known to have host plants restricted to genus Bidens. Further host specificity studies are required to evaluate the potential of this insect as a candidate for augmentative biological control agent for B. frondosa in Korea. All other insect species are either polyphagous or known crop pests.     

Cow dung extract: a medium for the growth of pseudomonads enhancing their efficiency as biofertilizer and biocontrol agent in rice

Some pseudomands are being utilized as biofertilizers and biopesticides because of their role in plant growth promotion and plant protection against root parasites, respectively. Two strains of Pseudomonas, P. jessenii LHRE62 and P. synxantha HHRE81, recovered from wheat rhizosphere, have shown their potential in field bioinoculation tests under rice-wheat and pulse-wheat rotation systems. Normally, pseudomonads are cultivated on synthetic media-like King’s B and used for inoculation on seeds/soil drench with talcum or charcoal as carrier material. Cow dung is being used for different purposes from the ancient time and has a significant role in crop growth because of the content in humic compounds and fertilizing bioelements available in it. Here, cow dung extract was tested as a growth medium for strains LHRE62 and HHRE81, in comparison with growth in King’s B medium. The log phase was delayed by 2 h as compared to growth in King’s B medium. The bacterial growth yield, lower in plain cow dung extract as compared to King’s B medium, was improved upon addition of different carbon substrates. Growth of rice var. Pant Dhan 4 in pot cultures was increased using liquid formulation of cow dung extract and bacteria as foliar spray, compared to their respective controls. Biocontrol efficacy of the bioagents was assessed by challenging rice crop with Rhizoctonia solani, a sheath blight pathogen. The growth promotion and biocontrol efficiencies were more pronounced in the case of mixed inocula of strains LHRE62 and HHRE81.     

Triazole substituted metal-free,metallo-phthalocyanines and their water soluble derivatives as potential cholinesterases inhibitors: Design,synthesis and in vitro inhibition study

In this study, 1,2,3-triazole substituted metal-free and metallo phthalocyanines (4, 5, 6) and their water soluble derivatives (4a, 5a, 6a) were designed, synthesized for the first time and tested in vitro on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Most phthalocyanines exhibited good inhibitory activities on these enzymes. Among the six phthalocyanines and starting compounds, 4a showed the most interesting profile as a submicromolar selective inhibitor of AChE (IC₅₀ = 0.040 µM) and 5a showed the most effective inhibitor of BChE (IC₅₀ = 0.1198 µM).     

Distribution of rotifers in North Island,New Zealand,and their potential use as bioindicators of lake trophic state

The distribution and ecology of planktonic rotifers was investigated in 33 lakes in the North Island, New Zealand, between 1997 and 1999. A total of 79 species of monogonont rotifer were identified, with an average of 21 species per lake, a diversity which is high in comparison with many previous New Zealand studies. Most species recorded were cosmopolitan taxa, and were widespread in their distribution over the North Island. Multivariate analyses (Multi-Dimensional Scaling and Canonical Correspondence Analysis) did not distinguish distinct lake groupings based on rotifer communities, but rather gradients in assemblages, which were most highly associated with lake trophic state. Based on these responses, the development of potential rotifer bioindicator schemes for lake trophic state is described and discussed.     

New benzoxazole derivatives as potential VEGFR-2 inhibitors and apoptosis inducers: design,synthesis, anti-proliferative evaluation,flowcytometric analysis,and in silico studies

A new series of benzoxazole derivatives were designed and synthesised to have the main essential pharmacophoric features of VEGFR-2 inhibitors. Cytotoxic activities were evaluated for all derivatives against two human cancer cell lines, MCF-7 and HepG2. Also, the effect of the most cytotoxic derivatives on VEGFR-2 protein concentration was assessed by ELISA. Compounds 14o, 14l, and 14b showed the highest activities with VEGFR-2 protein concentrations of 586.3, 636.2, and 705.7 pg/ml, respectively. Additionally, the anti-angiogenic property of compound 14b against human umbilical vascular endothelial cell (HUVEC) was performed using a wound healing migration assay. Compound 14b reduced proliferation and migratory potential of HUVEC cells. Furthermore, compound 14b was subjected to further biological investigations including cell cycle and apoptosis analyses. Compound 14b arrested the HepG2 cell growth at the Pre-G1 phase and induced apoptosis by 16.52%, compared to 0.67% in the control (HepG2) cells. The effect of apoptosis was buttressed by a 4.8-fold increase in caspase-3 level compared to the control cells. Besides, different in silico docking studies were also performed to get better insights into the possible binding mode of the target compounds with VEGFR-2 active sites.     

Synthesis and elaboration of N-methylpyrrolidone as an acetamide fragment substitute in bromodomain inhibition

N-Methylpyrrolidone is a solvent molecule which has been shown to compete with acetyl-lysine-containing peptides for binding to bromodomains. From crystallographic studies, it has also been shown to closely mimic the acetamide binding motif in several bromodomains, but has not yet been directly pursued as a fragment in bromodomain inhibition. In this paper, we report the elaboration of N-methylpyrrolidone as a potential lead in fragment-based drug design. Firstly, N-methylpyrrolidone was functionalised to provide points for chemical elaboration. Then, the moiety was incorporated into analogues of the reported bromodomain inhibitor, Olinone. X-ray crystallography revealed that the modified analogues showed comparable binding affinity and structural mimicry to Olinone in the bromodomain binding site.