Discovery of Novel Antiangiogenic Marine Natural Product Scaffolds

Marine natural products (MNPs) are recognized for their structural complexity, diversity, and novelty. The vast majority of MNPs are pharmacologically relevant through their ability to modulate macromolecular targets underlying human diseases. Angiogenesis is a fundamental process in cancer progression and metastasis. Targeting angiogenesis through selective modulation of linked protein kinases is a valid strategy to discover novel effective tumor growth and metastasis inhibitors. An in-house marine natural products mini-library, which comprises diverse MNP entities, was submitted to the Lilly’s Open Innovation Drug Discovery platform. Accepted structures were subjected to in vitro screening to discover mechanistically novel angiogenesis inhibitors. Active hits were subjected to additional angiogenesis-targeted kinase profiling. Some natural and semisynthetic MNPs, including multiple members of the macrolide latrunculins, the macrocyclic oxaquinolizidine alkaloid araguspongine C, and the sesquiterpene quinone puupehenone, showed promising results in primary and secondary angiogenesis screening modules. These hits inhibited vascular endothelial growth factor (VEGF)-mediated endothelial tube-like formation, with minimal cytotoxicity at relevant doses. Secondary kinase profiling identified six target protein kinases, all involved in angiogenesis signaling pathways. Molecular modeling and docking experiments aided the understanding of molecular binding interactions, identification of pharmacophoric epitopes, and deriving structure-activity relationships of active hits. Marine natural products are prolific resources for the discovery of chemically and mechanistically unique selective antiangiogenic scaffolds.     

Marine natural products as prototype agrochemical agents

In the interest of identifying new leads that could serve as prototype agrochemical agents, 18 structurally diverse marine-derived compounds were examined for insecticidal, herbicidal, and fungicidal activities. Several new classes of compounds have been shown to be insecticidal, herbicidal, and fungicidal, which suggests that marine natural products represent an intriguing source for the discovery of new agrochemical agents.     

Variance components,correlation and path analyses in cowpea (Vigna unguiculata L., Walp)

Journal of Crop Science and Biotechnology - Cowpea as a low-input crop has a potential to significantly ameliorate poor nutrition and food insecurity in sub-Sahara Africa if problem of poor seed...     

Impacts of long-term application of buctril super (bromoxynil) herbicide on microbial population,enzymes activity,nitrate nitrogen,Olsen-P and total organic carbon in soil

Long-term impact of buctril super (bromoxynil) herbicide in the wheat fields on soil microbial population, nitrate-N, Olsen-P, total organic carbon (TOC) and enzyme activities was evaluated in 18 sites in Pakistan. Nine sites were randomly selected from those places where bromoxynil herbicide had been used for the last 10 years designated as soil ‘X’ and other nine where no herbicide was used in that period designated as soil ‘Y’. Very importantly, it was found that long-term application of this herbicide in wheat fields reduced the actinomycetes and fungi population up to 19.7 and 14.3%, respectively, urease and dehydrogenase activity by 17.5 and 28.2%, respectively, and reduced nitrate-N, Olsen-P and TOC up to 55, 17 and 28.57%, respectively. Presence of high clay and organic matter contents enhanced the detrimental effect of herbicide by prolonging its persistence as compared to light-textured soils with low organic matter. As in Pakistan this herbicide is being used most frequently in wheat fields, data are scarce on the long-term effect of this herbicide on soil microbial activities and soil health. These findings could give new insights about the use of alternate herbicide in wheat fields, particularly in clay-textured and high organic matter contained soils for maintaining soil health.     

Arbuscular mycorrhizal fungi mitigates heavy metal toxicity adverse effects in sewage water contaminated soil on Tagetes erecta L

The aim of this experiment was to evaluate the impact of colonization with arbuscular mycorrhizal (AM) fungus Glomus constrictum on the biomass production, flower quality, chlorophyll content, macronutrients and heavy metals content of marigold (Tagetes erecta L.) planted under uncontaminated soil and watered with various rates of sewage water. Sewage water utilization significantly decreased biomass production, characters of flower, nutrient concentration and rates of mycorrhizal colonization of mycorrhizal (M) and non-mycorrhizal (NM) marigold as compared to control untreated plants especially at the higher rates, but the reduction rate was proportionally higher in non-AM treatments. Mycorrhizal plants had significantly greater yield, relative chlorophyll content, leaf area, flower quality and element (P, N, K and Mg) content compared to non-inoculated marigold plants irrigated with or without sewage water. Furthermore, AM inoculation had highly decreased heavy metal (Zn, Co, Mn, Cu) content in tissues as compared to equivalent non-inoculated plants grown under sewage water application. Growing marigold with AM inoculum can reduce toxicity of heavy metals and enhance biomass production and P uptake. The results support the view that AM have a protective function for the host plant, hence playing a potential function in soil polluted immobilization processes, and thus are of assessing the potential of phytoremediation of heavy metals in sewage water contaminated soil.     

Determination of baseline susceptibility of European populations of Tuta absoluta (Meyrick) to indoxacarb and chlorantraniliprole using a novel dip bioassay method

BACKGROUND: Tuta absoluta(Meyrick) is one of the most serious pests of tomato recently introduced in the Mediterranean region. A novel bioassay method designed for the accurate determination of insecticide toxicity on T. absoluta (IRAC method No. 022) was validated by three different laboratories [Greece (NAGREF), Italy (UC) and Spain (UPCT)] on European populations. RESULTS: The insecticides indoxacarb and chlorantraniliprole were used as reference products. The IRAC leaf dip method is easy to perform, producing repeatable, homogeneous responses. LC₅₀ values for indoxacarb ranged between 1.8 and 17.9 mg L^?1 (NAGREF), 0.93 and 10.8 mg L^?1 (UC) and 0.20 and 0.70 mg L^?1 (UPCT), resulting in a tenfold, 12‐fold and fourfold difference between the least and most susceptible populations at each laboratory respectively. For chlorantraniliprole, LC₅₀ values ranged between 0.10 and 0.56 mg L^?1 (NAGREF), 0.23 and 1.34 mg L^?1 (UC) and 0.04 and 0.24 mg L^?1 (UPCT), resulting in a sixfold difference in all three cases. Overall, UPCT reported lower mean LC₅₀ to indoxacarb, while UC reported higher LC₅₀ to chlorantraniliprole. CONCLUSIONS: The new bioassay is reliable, providing a useful tool in the design of IRM strategies. Within each country/lab, the variability observed in the results for both indoxacarb and chlorantraniliprole can be attributed to natural variation. Future research is necessary to determine the extent to which it is possible to compare results among laboratories. Copyright © 2012 Society of Chemical Industry     

Current Status on Marine Products with Reversal Effect on Cancer Multidrug Resistance

The resistance of tumor cells to a broad range of anticancer agents continues to be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR) is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp), ABCC1/multidrug resistance protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP). These transporters are part of the ATP-binding cassette (ABC) superfamily, whose members function as ATP-dependent drug-efflux pumps. Their activity can be blocked by various drugs such as verapamil (calcium channel blocker) and cyclosporin A (immunosuppressive agent), etc. These compounds are called MDR modulators or reversals. This review highlights several marine natural products with reversal effect on multidrug resistance in cancer, including agosterol A, ecteinascidin 743, sipholane triterpenoids, bryostatin 1, and welwitindolinones.     

Physiological and Molecular Analysis of Applied Nitrogen in Rice Genotypes

Ten genotypes of rice (Oryza sativa L.) were grown for 30 d in complete nutrient solution with 1 mmol/L (N-insufficient),4 mmol/L (N-moderate) and 10 mmol/L (N-high) nitrogen levels,and nitrogen efficiency (NE) was analyzed.Growth performance,measured in terms of fresh weight,dry weight and lengths of root and shoot,was higher in N-efficient than in N-inefficient rice genotypes at low N level.Of these 10 genotypes,Suraksha was identified as the most N-efficient,while Vivek Dhan the most N-inefficient.To find out the physiological basis of this difference,the nitrate uptake rate of root and the activities of nitrate assimilatory enzymes in leaves of N-efficient and N-inefficient rice genotypes were studied.Uptake experiments revealed the presence of two separate nitrate transporter systems mediating high-and low-affinity nitrate uptake.Interestingly,the nitrate uptake by the roots of Suraksha is mediated by both high-and low-affinity nitrate transporter systems,while that of Vivek Dhan by only low-affinity nitrate transporter system.Study of the activities and expression levels of nitrate assimilatory enzymes in N-efficient and N-inefficient rice genotypes showed that nitrate reductase (NR) and glutamine synthetase (GS) play important roles in N assimilation under low-nitrogen conditions.     

High-density growth and crude protein productivity of a thermotolerant Chlorella vulgaris: production kinetics and thermodynamics

Current study investigated the fermentative production of cell mass and crude protein using an axenic culture of the thermotolerant strain of Chlorella vulgaris grown mixotrophically in an illuminated 10-l glass bioreactor. The process was then upscaled to 1,000-l bioreactor. The organism supported maximum specific growth rate, crude protein volumetric productivity, and specific productivity of 1.2?day^?1, 2.26?g?l^?1?day^?1, and 0.76?g?g^?1?day^?1, respectively, with urea as nitrogen source. Gibbs free energy, enthalpy, and entropy values for its formation were 74.3, 56. 2?kJ?mol^?1, and ?59.1?J?mol^?1?K^?1, respectively, in both reactors and corresponded to those of thermotolerant organisms. Algal biomass grown in 10-l bioreactor contained 0.52?±?0.03, 12.6?±?2.0, 60.0?±?4.5, 0.4?±?0.02, 4.5?±?0.2, 12?±?0.5, and 3.81?±?0.5% carotenoids, carbohydrates, crude protein, DNA, RNA, lipids, and total chlorophyll, respectively. Dry biomass supported good growth of fish larvae comparable with that on commercial diet.