21 research outputs found
5,7-Dibromo-3-trifluoromethyl-3,4-dihydroacridin-1(2H)-one
In the title compound, C14H8Br2F3NO, the molecule is disordered across an approximate non-crystallographic mirror plane, which is in the plane of the fused ring system [The tetrahedral C atom bearing the trifluormethyl substituent is disordered with site occupancy factors of 0.80 (2) and 0.20 (2)]. In the crystal, a one-dimensional stacking of molecules involves interactions between the pyridine ring and symmetry-related Br and O atoms of adjacent molecules. The stacking distance between the mean planes of adjacent molecules is 3.395 (4) Å
In vitro anticancer screening of 24 locally used Nigerian medicinal plants
Background
Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods
The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results
Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 μg/ml. Conclusions
Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway
In vitro Anticancer Screening of 24 Locally Used Nigerian Medicinal Plants
Background: Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods: The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results: Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 g/ml. Conclusions: Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway.Chemistry and Chemical Biolog
Enantioselective Total Synthesis of (+)-Amabiline
The first total synthesis of (+)-amabiline, an unsaturated pyrrolizidine alkaloid from <i>Cynoglossum amabile</i>, is reported. This convergent, enantioselective synthesis proceeds in 15 steps (10-step longest linear sequence) in 6.2% overall yield and features novel methodology to construct the unsaturated pyrrolizidine or (−)-supinidine core
Visible-Light-Driven Photocatalytic Initiation of Radical Thiol–Ene Reactions Using Bismuth Oxide
A nontoxic and inexpensive
photocatalytic initiation of anti-Markovnikov
hydrothiolation of olefins using visible light is reported. This method
is characterized by low catalyst loading, thereby enabling a mild
and selective method for radical initiation in thiol–ene reactions
between a wide scope of olefins and thiols
Access to Highly Substituted 7‑Azaindoles from 2‑Fluoropyridines via 7‑Azaindoline Intermediates
A versatile
synthesis of 7-azaindoles from substituted 2-fluoropyridines
is described. C3-metalation and 1,4-addition to nitroolefins provide
substituted 2-fluoro-3-(2-nitroethyl)pyridines. A facile oxidative
Nef reaction/reductive amination/intramolecular S<sub>N</sub>Ar sequence
furnishes 7-azaindolines. Finally, optional regioselective electrophilic
C5-substitution (e.g., bromination or nitration) and subsequent in
situ oxidation delivers highly functionalized 7-azaindoles in high
overall efficiency
Covalent Enzyme Inhibition through Fluorosulfate Modification of a Noncatalytic Serine Residue
Irreversible enzyme
inhibitors and covalent chemical biology probes
often utilize the reaction of a protein cysteine residue with an appropriately
positioned electrophile (<i>e.g.</i>, acrylamide) on the
ligand template. However, cysteine residues are not always available
for site-specific protein labeling, and therefore new approaches are
needed to expand the toolkit of appropriate electrophiles (“warheads”)
that target alternative amino acids. We previously described the rational
targeting of tyrosine residues in the active site of a protein (the
mRNA decapping scavenger enzyme, DcpS) using inhibitors armed with
a sulfonyl fluoride electrophile. These inhibitors subsequently enabled
the development of clickable probe technology to measure drug-target
occupancy in live cells. Here we describe a fluorosulfate-containing
inhibitor (aryl fluorosulfate probe (FS-p1)) with excellent chemical
and metabolic stability that reacts selectively with a noncatalytic
serine residue in the same active site of DcpS as confirmed by peptide
mapping experiments. Our results suggest that noncatalytic serine
targeting using fluorosulfate electrophilic warheads could be a suitable
strategy for the development of covalent inhibitor drugs and chemical
probes
Near-Infrared Photoredox Catalyzed Tryptophan Functionalization for Peptide Stapling and Protein Labeling in Complex Tissue Environments
The chemical transformation of aromatic amino acids has emerged as an attractive alternative to non-selective lysine or cysteine labeling for the modification of biomolecules. However, this strategy has largely been limited by the scope of functional groups and biocompatible reaction conditions available. Herein, we report the implementation of near-infrared-activatable photocatalysts, TTMAPP and n-Pr-DMQA+, capable of generating fluoroalkyl radicals for selective tryptophan functionalization within simple and complex biological systems. At the peptide level, a diverse set of iodo-perfluoroalkyl reagents were used to install bioorthogonal handles for downstream applications or link inter- or intramolecular tryptophan residues for peptide stapling. We also found this photoredox transformation amenable to biotinylation of intracellular proteins in live cells for downstream confocal imaging and mass spectrometry-based analysis. Given the inherent tissue penetrant nature of near-infrared light we further demonstrated the utility of this technology to achieve photocatalytic protein fluoroalkylation in physiologically relevant tissue and tumor environments