The Total Syntheses of JBIR-94 and Two Synthetic Analogs and Their Cytotoxicities Against A549 (CCL-185) Human Small Lung Cancer Cells

We here disclose the total syntheses of the natural polyphenol JBIR-94 and two nonnatural analogs, whose structures are of interest for their bioactivity potential as radical scavengers. Although we initially attempted this by dually acylating both of putrecine’s amine nitrogens in a single pot, our endeavors with this method (which has been successfully reported by other groups) proved ineffectual. We accordingly opted for the lengthier approach of acylating each amine individually, which gratuitously prevailed and also aligns with separate literature precedent. Moreover, we here share our analysis of these target compounds’ cytotoxicities and IC50 values against A549 (CCL-185) human small lung cancer cells

The Total Syntheses of JBIR-94 and Two Synthetic Analogs and Their Cytotoxicities Against A549 (CCL-185) Human Small Lung Cancer Cells

We here disclose the total syntheses of the natural polyphenol JBIR-94 and two nonnatural analogs, whose structures are of interest for their bioactivity potential as radical scavengers. Although we initially attempted this by dually acylating both of putrecine’s amine nitrogens in a single pot, our endeavors with this method (which has been successfully reported by other groups) proved ineffectual. We accordingly opted for the lengthier approach of acylating each amine individually, which gratuitously prevailed and also aligns with separate literature precedent. Moreover, we here share our analysis of these target compounds’ cytotoxicities and IC50 values against A549 (CCL-185) human small lung cancer cells

Where is Nepal in the nutrition transition?

The patterns and trends of the Nutrition Transition in Nepal are unknown. This study aimed to identify where Nepal is in the nutrition transition. Time series data for 10 proxy variables of economic, demographic, dietary and epidemiological shifts were collected in five-year intervals from 1970 to 2010 from government and global databases. The structure of the Nepalese economy is gradually shifting from an agricultural to a modern industrial economy. Urbanisation and per capita income have increased. Nepalese dietary patterns have changed with plant fat and sugar as the main contributors to an increased energy and saturated fat trend. Life expectancy has increased and mortality and fertility have decreased. The double burden of disease is evident with the prevalence of underweight and many communicable diseases decreasing, while the prevalence of overweight/obesity and other non-communicable diseases is increasing. In conclusion, Nepal may be transiting from stage three (primarily rural poverty stricken areas) to stage four (mostly urban areas) of the Nutrition Transition. After the earthquake disaster on 25 April 2015, it is unclear whether this will change current nutrition transition trends/patterns and how long the recovery period will be

Cationic Anthraquinone Analogs as Selective Antimicrobials

Development of new antibiotics is always needed in the fight against growing threat from multiple drug–resistant bacteria, such as resistant Gram-negative (G−) Escherichia coli and Klebsiella pneumoniae . While the development of broad-spectrum antibiotics has attracted great attention, careful administration of these antibiotics is important to avoid adverse effects, like Clostridium difficile infection (CDI). The use of broad-spectrum antibiotics, for example, quinolones, can increase the risk of CDI by eradicating the protective bacteria in intestine and encouraging C difficile spore germination. Many common intestine bacteria are G− or anaerobic, including Enterococcus faecalis, Bacteroides fragilis , and E coli . Hence, it may be advantageous in certain therapeutic practices to employ selective antimicrobials. For instance, Gram-positive (G+) methicillin-resistant Staphylococcus aureus (MRSA) that can cause life-threatening sepsis can be controlled with the use of selective antibiotic, vancomycin. Nevertheless, its effectiveness has been limited with the emerging of vancomycin-resistant Staphylococcus aureus (VRSA). A recent report on antimicrobial cationic anthraquinone analogs (CAAs) that show tunable activity and selectivity may provide new hope in the search for selective antimicrobials. In particular, the lead CAA displays prominent activity against MRSA while manifesting low activity against E coli and low cytotoxicity toward normal mammalian cells

Fluorogenic probe for Detection of Hydrogen Sulfide in Living System

. We consider a network serving a patchwork of overlapping regions where jobs from a local region are assigned to a collection of local servers. Copies of these jobs are simultaneously queued at all the local servers. When a copy of the job begins service at one of the servers it is removed from the other queues. The system is equivalent to one in which the exact service requirement of each job is known at arrival time, and each job joins the local queue with the shortest waiting time. We describe how the amount of work in the network becomes large in the simple case of two servers, with one arrival stream for each server and a third, routeable arrival stream. If the proportion of routeable jobs is large enough then the waiting times at the servers become large in tandem when the total workload becomes large, thus delaying overload as long as possible. The fact that this resource pooling can be attained with a local routing policy not dependent on the state of the network has engineeri..

Mode of Action Study of Cationic Anthraquinone Analog: A New Class of Highly Potent Anti-cancer Agent

Previously, we reported the synthesis and structure–activity relationship (SAR) study of a series of novel 4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-3-ium salts, which had very potent anti-proliferative activities (low μM to nM GI50) against a broad range of cancer cells. These compounds, which can be viewed as cationic anthraquinone analogs (CAAs), are selective against cancer cells over bacteria or fungi as compared to the antibacterial CAAs that have also been reported by our group. Herein, we report a mode of action study of CAAs, which reveals that these compounds trigger apoptosis by generating extensive reactive oxygen species (ROS). The generation of extensive ROS causes oxidative stress, decrease in mitochondrial membrane potential, depletion of glutathione (GSH), and release of caspase-3, which ultimately kills cancer cells by programmed apoptosis. Furthermore, we have also shown that CAAs possess an 8-fold higher activity against the A549 cell line vs. the non-cancerous MRC-5 cell line

Antifungal Activities of 4”,6”-Disubstituted Amphiphilic Kanamycins

Amphiphilic kanamycins derived from the classic antibiotic kanamycin have attracted interest due to their novel bioactivities beyond inhibition of bacteria. In this study, the recently described 4″,6″-diaryl amphiphilic kanamycins reported as inhibitors of connexin were examined for their antifungal activities. Nearly all 4″,6″-diaryl amphiphilic kanamycins tested had antifungal activities comparable to those of 4″,6″-dialkyl amphiphilic kanamycins, reported previously against several fungal strains. The minimal growth inhibitory concentrations (MICs) correlated with the degree of amphiphilicity (cLogD) of the di-substituted amphiphilic kanamycins. Using the fluorogenic dyes, SYTOXTM Green and propidium iodide, the most active compounds at the corresponding MICs or at 2×MICs caused biphasic dye fluorescence increases over time with intact cells. Further lowering the concentrations to half MICs caused first-order dye fluorescence increases. Interestingly, 4×MIC or 8×MIC levels resulted in fluorescence suppression that did not correlate with the MIC and plasma membrane permeabilization. The results show that 4″,6″-diaryl amphiphilic kanamycins are antifungal and that amphiphilicity parameter cLogD is useful for the design of the most membrane-active versions. A cautionary limitation of fluorescence suppression was revealed when using fluorogenic dyes to measure cell-permeation mechanisms with these antifungals at high concentrations. Finally, 4″,6″-diaryl amphiphilic kanamycins elevate the production of cellular reactive oxygen species as other reported amphiphilic kanamycins