Synthesis and biological evaluation of 99mTc(CO)3(His–CB) as a tumor imaging agent

The chlorambucil l-histidine conjugate was synthesized and radiolabeled with [^99mTc(CO)₃]⁺ core to form the ^99mTc(CO)₃(His–CB) complex. The radiochemical purity of the complex was over 90%. It had good hydrophilicity and was stable at room temperature. The high initial tumor uptake with certain retention, fast clearance from background, good tumor/non-tumor ratios and satisfactory scintigraphic images highlighted the potential of ^99mTc(CO)₃(His–CB) as a tumor imaging agent.     

What makes a successful biocontrol agent? A meta-analysis of biological control agent performance

We qualitatively reviewed the biocontrol literature in two major journals, Biological Control and Environmental Entomology, over the past 10 years by scoring 878 studies into 11 biocontrol-oriented questions. Quantitative meta-analyses were then used on data from 145 studies to examine the effects of different types of biocontrol agents (parasitoids, predators, and pathogens) on several attributes of weed and pest populations. Results for our qualitative review showed that most biocontrol studies were focused on lepidopteran pests, and that parasitoids were the most common biocontrol agents used. Our quantitative review showed that, for weeds, biocontrol agents significantly reduced weed biomass (−82.0%), flower (−98.9%), and seed production (−89.4%). For pests, our quantitative review showed that biocontrol agents significantly reduced pest abundance by 130% compared to control groups, increased parasitism (+139.0%) and increased overall pest mortality (+159.0%) compared to targets not exposed to biocontrol agents. Effects on pest mortality tended to be stronger for parasitoids than predators, although reductions caused in pest abundance were much stronger when predators were used as biocontrol agents. Addition of two or more biocontrol agents increased mortality by 12.97% and decreased pest abundance by 27.17% compared to single releases. Separate sets of meta-analyses demonstrated that the negative impacts of biocontrol on non-target species were much smaller than those for target species, although adverse effects of biocontrol on non-target organisms are based on small sample sizes and should be interpreted with caution. Our results also showed that biocontrol efficacy tended to be higher when agents were generalists than when they were specialists. Large fail–safe numbers found for most of the estimated effects indicate the robustness of the results found for the efficacy of biological control programs.     

Is Puccinia xanthii a suitable biological control agent of Ambrosia artemisiifolia?

Common ragweed, Ambrosia artemisiifolia, is a highly allergenic North American plant that has become invasive in some parts of Europe, Asia and Australia following its introduction to many places in the world. Some earlier works suggested that a microcyclic autoecious rust fungus, Puccinia xanthii, known to infect A. artemisiifolia in the USA only, can be considered as a potential classical biocontrol agent (BCA) of this noxious weed in Europe and elsewhere. However, an extensive field survey did not reveal the presence of either P. xanthii or any other rusts on common ragweed in 14 US states and two Canadian provinces in 2002 and 2003. Moreover, P. xanthii infecting A. artemisiifolia has never been recorded in Canada, although it is known to occur on A. trifida and Xanthium spp. there. Nevertheless, herbarium specimens collected between 1855 and 1963 in five states of the USA confirmed the presence of P. xanthii on A. artemisiifolia. It is concluded that currently P. xanthii cannot be regarded as a promising BCA of A. artemisiifolia, although it did occur on common ragweed at least a few decades ago in the USA and some forms of this rust species have already been evaluated as effective BCAs of Xanthium in Australia.     

Laboratory host range testing of Lilioceris sp. near impressa (Coleoptera: Chrysomelidae) – a potential biological control agent of air potato,Dioscorea bulbifera (Dioscoreaceae)

Air potato, Dioscorea bulbifera, is an invasive, herbaceous, climbing vine, which dominates invaded native vegetation in Florida. The fortuitous discovery of Lilioceris sp. near impressa defoliating D. bulbifera vines and feeding on the bulbils (aerial tubers) in the Katmandu Valley of Nepal initiated a project to assess the potential of this leaf beetle for biological control of air potato in Florida. Quarantine host specificity tests were conducted on 41 plant species in 24 families and 13 orders, with 26 species outside of the Dioscoreaceae and 15 species within the Dioscoreaceae. Adults test fed (nibbled) on 4/12 of tested Dioscorea species, but no larval feeding or development occurred on any plant other than the target, D. bulbifera. The larvae feed gregariously and quickly skeletonize offered leaves of air potato. Air potato bulbils that received any feeding damage to the primary meristematic region did not sprout. The ability of the beetle larvae and adults to feed on the bulbils is important because in Florida, the plant rarely flowers or produces fruit, so these aerial tubers are the primary means of persistence and spread. The adults can live for several months without food. This extremely specialized herbivore from part of the weed's native range appears to have great promise as a biological control of air potato.     

Synthesis and biological evaluation of Germanium(IV)–polyphenol complexes as potential anti-cancer agents

Germanium (Ge) is considered to play a key role in the pharmacological effects of some medicinal plants. Here, two new Ge(IV)–polyphenol complexes were synthesized and measured for their potential biological activities. The results indicated that these Ge(IV)–polyphenol complexes possessed great anti-oxidative activities, both showing stronger hydroxyl scavenging effects than their corresponding ligands. We also demonstrated the strong intercalating abilities of Ge(IV)–polyphenol complexes into calf thymus-DNA molecules. In addition, these two Ge(IV)–polyphenol complexes showed strong proliferative inhibition effect on HepG2 cancer cells. Moreover, the morphological changes in HepG2 cells induced by Ge(IV)–polyphenol complexes were detected by atomic force microscopy. All these results collectively suggested that Ge(IV)–polyphenol complexes could be served as promising pharmacologically active substances against cancer treatment.     

Laboratory host range testing of Neomusotima conspurcatalis (Lepidoptera: Crambidae) – a potential biological control agent of the invasive weed,Old World climbing fern,Lygodium microphyllum (Lygodiaceae)

Old World climbing fern, Lygodium microphyllum, is a serious invasive weed in south Florida. Development of biological control is vital for sustainable management of L. microphyllum. Neomusotima conspurcatalis was discovered in Hong Kong in 1997 and was subsequently found causing feeding damage on L. microphyllum in much of its native range in Asia. Quarantine testing of N. conspurcatalis used 37 non-Lygodium fern species representative of New World genera of cultivated ferns and fern allies, one gymnosperm, three crop species, six Lygodium species, and the primary host L. microphyllum. No significant oviposition or feeding was observed on any of the 41 non-Lygodium species evaluated. Oviposition and feeding occurred on all Lygodium species, but amounts were low and usually significantly less than observed on L. microphyllum. The exception was L. japonicum, which was preferred as an oviposition host. Neomusotima conspurcatalis was only able to complete development on L. japonicum and L. palmatum, but survival on these species was only half that occurring on L. microphyllum. Neomusotima conspurcatalis is a Lygodium specialist. Lygodium japonicum is an invasive weed in the United States. Lygodium palmatum is restricted to areas of the United States where freezing winter temperatures would be lethal to N. conspurcatalis. It was concluded that N. conspurcatalis would pose no threat to native or cultivated plants in North America or the Caribbean and should be considered for biocontrol of L. microphyllum. A release petition was submitted in 2005. An USDA-APHIS release permit for N. conspurcatalis was issued in 2007.     

Monitored releases of Rhinoncomimus latipes (Coleoptera: Curculionidae), a biological control agent of mile-a-minute weed (Persicaria perfoliata), 2004–2008

Mile-a-minute weed, Persicaria perfoliata (L.) H. Gross, is an invasive annual vine of Asian origin that has developed extensive monocultures, especially in disturbed open areas in the Mid-Atlantic region of the United States. A host-specific Asian weevil, Rhinoncomimus latipes Korotyaev, was approved for release in North America in 2004, and weevils have been reared at the New Jersey Department of Agriculture Beneficial Insect Laboratory since then. By the end of 2007 more than 53,000 weevils had been reared and released, mostly in New Jersey, but also in Delaware, Maryland, Pennsylvania, and West Virginia. The beetles established at 63 out of 65 sites (96.9%) where they were released between 2004 and 2007, with successful releases consisting of as few as 200 weevils. Weevils were recorded at 30 additional non-release sites in New Jersey, where they had dispersed at an average rate of 4.3 km/year. Standardized monitoring of fixed quadrats was conducted in paired release and control sites at eight locations. Significant differences in mile-a-minute weed populations in the presence and absence of weevils were found at three locations, with reduction in spring densities to 25% or less of what they had been at the start within 2–3 years at release sites, while weed densities at control sites were largely unchanged. Mile-a-minute weed populations at a fourth site were similarly reduced at the release site, but without control data for comparison due to rapid colonization of the paired control site. At the other four locations, all on islands, mile-a-minute weed populations were reduced at both release and control sites without large weevil populations developing, apparently due to environmental conditions such as late frost and extreme drought.     

Synthesis and in vitro and in vivo evaluation of manganese(III) porphyrin–dextran as a novel MRI contrast agent

5-(4-Aminophenyl)-10,15,20-tris(4-sulfonatophenyl) manganese(III) porphyrin conjugated with dextran was synthesized. Its potential of being used as a tumor-targeting magnetic resonance imaging contrast agent was evaluated in vitro and in vivo. The results demonstrated that the compound has a longitudinal relaxivity (R₁) higher than Gd-DTPA, low cytotoxicity and binding specificity to tumor cell membrane.     

Can Beauveria bassiana Bals. (Vuill) (Ascomycetes: Hypocreales) and Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) be used together for improved biological control of Bactericera cockerelli (Hemiptera: Triozidae)?

Bactericera cockerelli (Sulc.) is an important pest of solanaceous crops and a vector of the pathogen Candidatus Liberibacter psyllaurous. Biocontrol of this pest has been attempted with either entomopathogenic fungi or the parasitoid Tamarixia triozae (Burks), but prior to this study, their potential impact in combination had not been studied. The aim of the present study was to evaluate T. triozae parasitism rates on B. cockerelli nymphs that were previously infected for different periods of time by three isolates of Beauveria bassiana (Bals.) Vuill. Two native isolates (BB40 and BB42) and one commercial isolate (GHA) were used. The virulence of these isolates was first estimated against B. cockerelli and T. triozae. LC₅₀ values for the native isolates BB40 and BB42 against B. cockerelli were 9.5 × 10⁵ and 2.42 × 10⁶ conidia mL⁻¹ respectively; they were significantly more virulent than isolate GHA with an LC₅₀ of 1.97 × 10⁷ conidia mL⁻¹. However, isolate GHA was significantly more virulent against T. triozae with an LC₅₀ of 1.11 × 10⁷ conidia mL⁻¹ compared with LC₅₀s of 1.49 × 10⁷ and 1.14 × 10⁸ conidia mL⁻¹ for the native isolates BB40 and BB42 respectively. Groups of nymphs were then inoculated with LC₂₀, LC₅₀ or LC₉₀ concentrations of each isolate and presented to T. triozae as hosts either on the day of inoculation or 1, 2, 3, 4, 5, 6 days after inoculation. Subsequent levels of parasitism were recorded. Overall, parasitism rates were similar in inoculated and control nymphs. No parasitism occurred in nymphs 6 days after fungal inoculation. Parasitoids used to parasitize uninoculated B. cockerelli nymphs survived significantly longer (7.8 days) than parasitoids that had been used to parasitize fungus-inoculated nymphs (7.3 days). This suggests an inability of the parasitoid to avoid infection when foraging on inoculated nymphs. In conclusion, although the parasitism rate in control and fungus-treated nymphs was similar, suggesting a combination of both biological control agents is possible, we believe there are also negative implications for the parasitoid because its survival was greatly reduced after attacking infected nymphs.     

Structure based molecular design, synthesis and biological evaluation of α-pyrone analogs as anti-HSV agent

Several options for treating Herpes Simplex Virus type 1 and type 2 are available. However, non-specific inhibition and drug resistance warrants the discovery of new anti-herpetic compounds with better therapeutic profile or different mode of action. The non-nucleoside inhibitors of HSV DNA polymerase target the site that is less important for the binding of a natural nucleoside or nucleoside inhibitors. In the present study, we have explored the possibility to find a new lead molecule based on α-pyrone analogs as non-nucleoside inhibitors using structure based modeling approach. The designed molecules were synthesized and evaluated for anti-HSV activity using MTT assay. The compound 5h with EC(50) 7.4μg/ml and CC(50) 52.5μg/ml was moderately active against HSV when compared to acyclovir. A plaque reduction assay was also carried out and results reveal that 5h is more effective against HSV-1 with better selective index of 12.8 than against HSV-2 (SI=3.6). The synthesized compounds were also evaluated for anti-HIV activity, but none were active.     

Effect of temperature on the larval stage of Tetanocera elata (Diptera: Sciomyzidae) – Potential biological control agent of pestiferous slugs

Due to the considerable losses caused by slugs in terms of agricultural production and revenue, there is an urgent need for a cost effective biological control agent. The malacophagous nature of the sciomyzid fly, Tetanocera elata (Fab.) makes it a possible contender to meet this demand. This study examined the effect of constant temperatures (14, 17, 20, 23, and 26 °C), in addition to ambient outdoor and laboratory temperatures on T. elata larval duration and predation. In general, the mean and median larval stage duration decreased as temperature increased with percentage survival for the overall larval stage (62%) greatest at 20 °C with a median duration of 44 days. There was no significant difference between temperatures with regard to the number of slugs killed per larva and while predation rate increased with increasing constant temperature, there was also no significant difference between the constant temperatures. Our results show that puparial weight can be used to predict the sex of adult flies prior to their emergence. The results are discussed in the context of the suitability of T. elata as a biological control agent of pestiferous slugs.     

Temperature and the biology and predation of Ilione albiseta (Diptera: Sciomyzidae) — Potential biological control agent of liver fluke

The effect of temperature on predation by Ilione albiseta (Diptera: Sciomyzidae) on Lymnaea peregra was investigated at 14°, 17°, 20°, 23° and 26°C. The mean dry weight of snail tissue (Lymnaea peregra) attacked and consumed per day by first and second instar I. albiseta larvae was highest at 20°C while for third instar and total larval duration period it was greatest at 23°C. The mean number of snails killed per day during the third instar was also highest at 23°C. The total amount of snail tissue consumed by I. albiseta larvae increased significantly from first to second instar and from second to third instar at each constant temperature. Mean survival period of unfed first instar larvae decreased from 28.4 days at 14°C to 11 days at 26°C and the mean length of the second instar cephalopharyngeal skeleton decreased with increasing temperatures. As temperature increased the rate of consumption of oxygen (dissolved in water) by first and third instar larvae rose.     

Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships

The aromathecin topoisomerase I (top1) inhibitors offer promising scaffolds for the development of novel cancer chemotherapeutics. They are ‘composites’ of the camptothecin and indenoisoquinoline top1 inhibitors. Interestingly, some structure–activity relationship (SAR) overlap between the aromathecins and the indenoisoquinolines has been observed. For both classes, placement of certain polar groups in similar regions of the heteroaromatic system improves top1 inhibitory and antiproliferative activities. A series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths has been prepared. These compounds all possess similar antiproliferative potency, but a general trend is observed: aromathecins with longer diaminoalkane substituents (>6 carbons) possess lower anti-top1 activity than their smaller counterparts (2–4 carbons), presumably as a result of unfavorable hydrophobic interactions. This trend is also noted with the indenoisoquinolines, revealing additional SAR overlap that supports the hypothesis that there is a ‘universal’ top1 inhibitor SAR.     

Design,synthesis and biological evaluation of estradiol–chlorambucil hybrids as anticancer agents

A series of estradiol–chlorambucil hybrids was synthesized as anticancer drugs for site-directed chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of estrone at position 16α of the steroid nucleus. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent breast cancer cell lines. The novel hybrids showed significant in vitro anticancer activity when compared to chlorambucil. Structure–activity relationship (SAR) reveals the influence of the length of the spacer chain between carrier and drug molecule.     

Design,synthesis and biological evaluation of metronidazole–thiazole derivatives as antibacterial inhibitors

A series of metronidazole–thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, ¹H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5e exhibited the most potent inhibitory activity against E. coli FabH with IC₅₀ of 4.9 μM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5a, 5b, 5d, 5e, 5g and 5i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.     

Design,synthesis, and biological evaluation of dihydroartemisinin–fluoroquinolone conjugates as a novel type of potential antitubercular agents

Tuberculosis remains a global public health problem in recent years. To develop novel type of potential antitubercular agents, twelve novel dihydroartemisinin–fluoroquinolone (DHA–FQ) conjugates (three types of molecules) were gradually designed and conveniently synthesized. All the newly synthesized conjugates were well characterized and evaluated against different Mycobacterium tuberculosis strains in vitro. The screening results showed that five DHA–FQ conjugates were active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest inhibitory activity (MIC = 0.0625 μg/mL), which was comparable to the positive control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also displayed comparable activities against various clinically isolated sensitive and resistant M. tuberculosis strains (MIC = 0.125–16 μg/mL) to Moxifloxacin. All target compounds possessed selective anti-M. tuberculosis ability. Preliminary structure–activity relationship demonstrated that short linker between DHA and FQ was favorable for strong antitubercular activity. This study provides a new clue for the development of novel antitubercular lead molecules.     

Similar experiment – different conclusion; a response to the recent proposition of Septoria lepidii as a potentially important biological control agent for weedy species of Lepidium in North America

Following preliminary host-specificity testing Septori lepidii Desm. was recently proposed as a potentially important biological control agent for invasive Lepidium species in North America. Conversely, a previous, unpublished assessment of S. lepidii for biocontrol of Lepidium latifolium found the pathogen to be unsuitable due to infection of the American native Lepidium huberi.     

Life cycle assessment of California processing tomato: an evaluation of the effects of evolving practices and technologies over a 10-year (2005–2015) timeframe

Purpose

California is the largest US producer of processing tomatoes, generating 96% of all domestic production and nearly 30% of global supply. Processing tomatoes are mostly processed into diced and paste products. Consumers and actors along their supply chains are increasingly interested in understanding their environmental burdens and identifying opportunities for improvements. This study applies life cycle assessment (LCA) to California diced and paste products over a 10-year timeframe to characterize current impacts and historical trends.

Methods

The LCA considers a scope from cradle-to-processing facility gate and accords with relevant Product Category Rules as published by the International EPD® System. Extensive primary data were collected for tomato cultivation for the years 2005 and 2015, and from processing facilities for 2005, 2010, and 2015 to understand the effects of evolving practices and technologies. We estimate crop and regional specific nitrous oxide and nitrate leaching emissions using a biogeochemical model, and the USES-LCA model is used to determine potential impacts from pesticide application. A suite of impact assessment categories is included based on the CML method (only global warming potential and freshwater consumption values are in the abstract).

Results and discussion

The 2015 results of the study indicate that diced tomatoes are responsible for 0.16 kg CO₂e and 71 L of freshwater per kg, and paste is responsible for 0.83 kg CO₂e and 328 L of freshwater per kg. The main opportunities for improvement include natural gas use in the greenhouse phase, energy for irrigation pumping and fertilizer type in the cultivation phase, and natural gas and electricity use in the facility processing phase. These hotspots are consistent with studies of processing tomato in other parts of the world. Evaluating trends over time showed that technological improvements in the industry had reduced life cycle impacts; for example, global warming potential decreased by 12% for paste and 26% for diced products between 2005 and 2015.

Conclusions

Trends over time show increasing efficiency at the cultivation and processing facility stages that have led to reductions in all impact categories evaluated. However, additional opportunities exist beyond efficiency improvements. Fertilizer and pesticide choice are potential opportunities for further reducing impacts. Also, the introduction of renewables in each phase of the supply chain (solar-powered irrigation pumps and onsite solar energy generation for facilities) could reduce the overall supply chain GWP₁₀₀ impacts by 9–10%.