New One-Pot Methodologies for the Modification or Synthesis of Alkaloid Scaffolds

There are several avenues by which promising bioactive natural products can be produced in sufficient quantities to enable lead optimization and medicinal chemistry studies. The total synthesis of natural products is an important, but sometimes difficult, approach and requires the development of innovative synthetic methodologies to simplify the synthesis of complex molecules. Various classes of natural product alkaloids are both common and widely distributed in plants, bacteria, fungi, insects and marine organisms. This mini-review will discuss the scope, mechanistic insights and enantioselectivity aspects of selected examples of recently developed one-pot methods that have been published in 2009 for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and γ-lactams. In addition, progress on the synthesis of β-carboline (manzamine) alkaloids will also be discussed

The High School in the Middle of Everywhere: Nebraska’s Lincoln High

In 2002, world-renowned author Mary Pipher published a book about her home city, Lincoln Nebraska, playfully titled “The Middle of Everywhere” a tongue-in-cheek rejoinder to the idea that Nebraska is ‘the middle of nowhere.’ But word play aside, her title was empirically apt, as her volume documented how immigration and refugee resettlement were demographically transforming Nebraska’s capital city. As in other cities, resettlement was concentrated in some areas of Lincoln, placing differential burdens on different parts of the community’s institutional infrastructure. Of interest to readers of this volume, Lincoln’s refugees and immigrants were concentrated in the city’s oldest high school. This account shares how that school embraced the challenges of demographic change by valuing the knowledge, skills and experience of students and their families

Structure identification of potential compound as selective renal anticancer isolated from Nerium indicum Mill. Leaves

Oleandrin is one of cardenolida compound isolated from an active fraction of Nerium indicum Mill leaves. (fam. Apocynaceae), which have cytotoxic effect on several human cancer cells, and also to normal cells in vitro. Another compound which was potential as renal anticancer has also been isolated from N. indicum. However, its chemical structure has not been discovered. The aim of this study was to identify the potential compound as selective to renal cancer present in the leaves of N. indicum.The potential compound was isolated from the active fraction using Preparative TLC and structure elucidation was done by using spectroscopic methods (UV, IR, MS and NMR).Base on this spectra and by comparison with oleandrin data, it was indicated that the potential compound as Renal anticancer was as 16,17-dehydrodeacetyl-5a-oleandrin.Key word: N.indicum, oleandrin, cytotoxic, renal anticancer, spectroscopi

Monanchocidin A From Subarctic Sponges of the Genus Monanchora and Their Promising Selectivity Against Melanoma in vitro

© Copyright © 2020 Gogineni, Oh, Waters, Kelly, Stone and Hamann. Marine sources have long been known for their potential to produce unique skeletons and various biological activities. Fractionation of the ethanol extracts of an undescribed species of Monanchora Carter, 1883 and a specimen closely comparable to Monanchora pulchra (Lambe, 1894/1895) (Class Demospongiae, Order Poecilosclerida, Family Crambeidae), yielded a known compound, monanchocidin A. Monanchocidin A, a secondary metabolite, showed very modest antibacterial, antifungal, and antiprotozoal activities with IC50 values ranging between 255.75 and 7288.92 μM. Monanchocidin A also exhibited potent selective activity for the melanoma panel in the NCI cancer cell screening panel

Phalerin, a new benzophenoic glucoside isolated from the methanolic extract of Mahkota Dewa [Phaleria macrocarpa (scheff). Boerl.] leaves

Mahkota Dewa [Phaleria macrocarpa (Scheff). Boerl.] is used traditionally to treat cancers in Indonesia. Extract methanol of the leaves displayed a small LC50 value (63.16 μg/ml) on BST (Brine Shrimp Lethality test) assay; therefore a phytochemical study of this extract was undertaken. A new benzophenoic glucoside was isolated from the methanol extract and identified as 4,5-dihydroxy,4’-methoxybenzophenone-3-0-β-D-glucoside (Phalerin) based on its spectroscopic data. Phalerin was cytotoxic to myeloma cell line (NS-1) (in vitro) having IC50 of 83 μg/ml or 1.9 x 10-1 mM.Key words: Phaleria macrocarpa, Phalerin, myelom

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

In order to expand the repertoire of antifungal compounds a novel, high-throughput phenotypic drug screen targeting fungal phosphatidylserine (PS) synthase (Cho1p) was developed based on antagonism of the toxin papuamide A (Pap-A). Pap-A is a cyclic depsipeptide that binds to PS in the membrane of wild-type Candida albicans, and permeabilizes its plasma membrane, ultimately causing cell death. Organisms with a homozygous deletion of the CHO1 gene (cho1ΔΔ) do not produce PS and are able to survive in the presence of Pap-A. Using this phenotype (i.e. resistance to Pap-A) as an indicator of Cho1p inhibition, we screened over 5,600 small molecules for Pap-A resistance and identified SB-224289 as a positive hit. SB-224289, previously reported as a selective human 5-HT1B receptor antagonist, also confers resistance to the similar toxin theopapuamide (TPap-A), but not to other cytotoxic depsipeptides tested. Structurally similar molecules and truncated variants of SB-224289 do not confer resistance to Pap-A, suggesting that the toxin-blocking ability of SB-224289 is very specific. Further biochemical characterization revealed that SB-224289 does not inhibit Cho1p, indicating that Pap-A resistance is conferred by another undetermined mechanism. Although the mode of resistance is unclear, interaction between SB-224289 and Pap-A or TPap-A suggests this screening assay could be adapted for discovering other compounds which could antagonize the effects of other environmentally- or medically-relevant depsipeptide toxins

HPLC Plasma Assay of a Novel Anti-MRSA Compound, Kaempferol-3-O-Alpha-L-(2 \u27\u27,3 \u27\u27-di-p-coumaroyl)rhamnoside, from Sycamore Leaves

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen that is resistant to current antibiotic therapy. Thus, there is an urgent need for novel antimicrobial agents that can effectively combat these new strains of drug-resistant superbugs . Recently, fractionation of an extract from Platanus occidentalis (American sycamore) leaves produced an active kaempferol molecule, 3-O-alpha-L-(2 ,3 -di-p-coumaroyl)rhamnoside (KCR), in four isomeric forms; all four isomers exhibit potent anti-MRSA activity. In order to further the preclinical development of KCR as a new antibiotic class, we developed and validated a simple analytical method for assaying KCR plasma concentration. Because KCR will be developed as a new drug, although comprising four stereoisomers, the analytical method was devised to assay the total amount of all four isomers. In the present work, both a plasma processing procedure and an HPLC method have been developed and validated. Mouse plasma containing KCR was first treated with ethanol and then centrifuged. The supernatant was dried, suspended in ethanol, centrifuged, and the supernatant was injected into an HPLC system comprising a Waters C18, a mobile phase composing methanol, acetonitrile, and trifluoroacetic acid and monitored at 313 nm. The method was validated by parameters including a good linear correlation, a limit of quantification of 0.27 μg/mL, and high accuracy. In summary, this method allows a rapid analysis of KCR in the plasma samples for pharmacokinetics studies

High Metal Enrichments in Luminous Quasars

We discuss observations of the broad emission line in luminous intermediate redshift quasars, with emphasis on Q0207 -398. This object has relatively sharp lines, allowing us to deconvolve the profiles into distinct components. In this paper we examine the high ionization region, which we show must be matter-bounded, partially transparent to ionizing radiation. We measure a large N V λ1240/He II λ1640 ratio in Q0207-398, but detailed calculations predict this ratio to be ~1 for standard cloud properties. We show that no choice of incident continuum, ionizing photon flux, density, or even the appeal to nonradiative energy sources, can reproduce the observed N V, C IV, O VI, He II spectrum with solar abundances. The intensity of the N V line is sensitive to the abundance of the gas because the abundance of nitrogen, a secondary element goes up roughly as the square of the metallicity. The lowest metallicity capable of reproducing the N V spectrum in Q0207 - 398 is Z ~ 5 Z☉, consistent with that inferred to exist in the cores of massive galaxies after epochs of rapid star formation. Our final model of the high-ionization emission region is one with many properties similar to those inferred for broad absorption-line QSO absorption-line clouds

EVALUATION OF THREE MEDICINAL PLANT EXTRACTS AGAINST PLASMODIUM FALCIPARUM AND SELECTED MICROGANISMS

Background: A great revival of scientific interests in drug discovery has been witnessed in recent years from medicinal plants for health maintenance. The aim of this work was to investigate three Nigerian medicinal plants collected in Nigeria for their in vitro antiplasmodial and antimicrobial activities. Materials and Methods: Extracts obtained from parts of Persea americana, Jatropha podagrica and Picralima nitida and their fractions were evaluated for in vitro antiprotozoal and antimicrobial activity. Result: The methanol extract of P. nitida demonstrated activity against chloroquine-sensitive and chloroquine-resistant P. falciparum clones with IC50 values of 6.3 and 6.0 µg/mL, respectively. Methanol and chloroform extracts of P. americana seed showed antifungal activity against Cryptococcus neoformans IC50 less than 8 and 8.211 µg/mL respectively. Finally, the petroleum ether extract of P. americana had activity against methicillin-resistant Staphylococcus aureus (MRSA) with an IC50 value of 8.7 µg/mL. Conclusion: The study revealed the antibacterial and antiplasmodial activities of the plants extracts at the tested concentrations