Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

Examining the Impact of Patch Burning on Livestock Grazing Patterns in Edwards Plateau, Texas

Production of sheep, goat, and cattle are major agricultural enterprises on West Texas rangelands, especially in the Edwards Plateau. In this region, the use of fire as a management tool was suppressed until recently. Although previous studies have been conducted to evaluate cattle use of burned versus unburned patches, there has been a lack of studies where combinations of livestock species grazing together on patch burned areas have been evaluated. The objective of this study is to examine grazing patterns of cattle, sheep and goats, both spatially and temporally, on areas where patch burning has been implemented. The study site is the Texas A&M AgriLife Research Ranch, Martin Ranch, located in Mesquite-Oak-Savanna ecosystem in Menard County of Texas, USA. In February 2019 and September 2020, patch burns were implemented on the ranch and represented about 29% of the total ranch area (480 out of 1655 ha). After the burns, animals from the resident herd were randomly selected and GPS collars were placed on 34 goats, 33 sheep, and 8 cows to reflect the proportion of animals in the resident herd. The GPS collars were set to collect movement data every 10 minutes during a fourteen-month period. Gates and fences for the entire ranch were opened and livestock were free to choose areas to graze. Data from the GPS’s were evaluated to determine locations where the animals grazed and their preferences for different areas of the landscape. Initial observations indicate that cattle and sheep were more attracted by recent burned patches compared to goats. Livestock forage use patterns and time spent by species in the burned and unburned areas and among different vegetation land cover classes are presented. Information from this study will assist in providing information to producers on how implementation of patch burning would influence their management of these grazing lands

In vitro metabolism of the synthetic cannabinoid 3,5-AB-CHMFUPPYCA and its 5,3-regioisomer and investigation of their thermal stability.

Recently, the pyrazole-containing synthetic cannabinoid N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) has been identified as a 'research chemical' both in powdered form and as an adulterant present in herbal preparations. Urine is the most common matrix used for abstinence control and the extensive metabolism of synthetic cannabinoids requires implementation of targeted analysis. The present study describes the investigation of the in vitro phase I metabolism of 3,5-AB-CHMFUPPYCA and its regioisomer 5,3-AB-CHMFUPPYCA using pooled human liver microsomes. Metabolic patterns of both AB-CHMFUPPYCA isomers were qualitatively similar and dominated by oxidation of the cyclohexylmethyl side chain. Biotransformation to monohydroxylated metabolites of high abundance confirmed that these species might serve as suitable targets for urine analysis. Furthermore, since synthetic cannabinoids are commonly administered by smoking and because some metabolites can also be formed as thermolytic artefacts, the stability of both isomers was assessed under smoking conditions. Under these conditions, pyrolytic cleavage of the amide bond occurred that led to approximately 3 % conversion to heat-induced degradation products that were also detected during metabolism. These artefactual 'metabolites' could potentially bias in vivo metabolic profiles after smoking and might have to be considered for interpretation of metabolite findings during hair analysis. This might be relevant to the analysis of hair samples where detection of metabolites is generally accepted as a strong indication of drug use rather than a potential external contamination. Copyright © 2016 John Wiley & Sons, Ltd

Forage Monitoring Technology to Improve Risk Management Decision Making by Herders in the Gobi Region of Mongolia

In the period from 1999 to 2002, Mongolia experienced a series of droughts and severe winters that lowered livestock numbers by approximately 30% countrywide. In the Gobi region, livestock mortality reached 50% with many households losing entire herds (Siurua & Swift 2002). In March 2004, a program was initiated by the United States Agency for International Development (USAID) through the Global Livestock Collaborative Research and Support Program (GLCRSP). The goal of this program is to develop forage monitoring technologies that provide early warning of drought and winter disaster to improve livestock herder decision making in the Gobi region. The program has two major objectives: (1) to develop a regional forage monitoring system that provides near-real time spatial and temporal assessment of current and forecasted forage conditions, and (2) to develop a communication infrastructure that provides herders with data on forage conditions to assist them in making timely and specific management decisions