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European Journal of Medicinal Chemistry Nov 2021Given the increasing reports of well-defined bimetallic molecular complexes as potential anticancer agents in the last decades, along with the prevalence of platinum in... (Review)
Review
Given the increasing reports of well-defined bimetallic molecular complexes as potential anticancer agents in the last decades, along with the prevalence of platinum in anticancer therapy, we report here a detailed survey of bimetallic platinum and palladium complexes investigated as potential anticancer agents. Specifically, we will concentrate on the synthesis, characterisation and biological (anticancer) studies of a sub-class of these agents, namely homo and heterobimetallic complexes bearing a bridging phosphane ligand of the type: [LM(μ-RP(CH)PR)ML] (where M is platinum or palladium, M is any other transition metal, R = alkyl or aryl substituents, L or L are co-ligands, n = 1-6). We will review the in vitro and in vivo activities and any mechanistic anticancer studies of these complexes with a view of trying to delineate patterns in biological activity and structure-activity relationships (SAR). We do not include the review of bimetallic complexes in this class that have not undergone any anticancer testing, nor those that have been involved in other biological investigations unrelated to cancer studies.
Topics: Animals; Antineoplastic Agents; Cell Survival; Coordination Complexes; Humans; Ligands; Palladium; Phosphines; Platinum; Structure-Activity Relationship
PubMed: 34214843
DOI: 10.1016/j.ejmech.2021.113651 -
BMJ Case Reports Oct 2013Acute intoxication from the pesticide aluminium phosphide is a relatively rare, life-threatening condition in which cardiovascular decompensation is the most feared... (Review)
Review
Acute intoxication from the pesticide aluminium phosphide is a relatively rare, life-threatening condition in which cardiovascular decompensation is the most feared problem. We report the case of a patient exposed to aluminium phosphide-liberated phosphine gas. It resulted in the development of a gastroenteritis-like syndrome accompanied by severe reduction in white blood cell numbers as an early and prominent manifestation. By affecting important physiological processes such as mitochondrial function and reactive oxygen species homeostasis, phosphine could cause severe toxicity. After presenting the characteristics of certain leucocyte subpopulations we provide the current molecular understanding of the observed leukopenia which in part seems paradoxical.
Topics: Accidents, Home; Aluminum Compounds; Blood Chemical Analysis; Emergency Service, Hospital; Follow-Up Studies; Greece; Humans; Leukopenia; Male; Middle Aged; Pesticides; Phosphines; Risk Assessment
PubMed: 24172776
DOI: 10.1136/bcr-2013-201229 -
Molecules (Basel, Switzerland) Mar 2023Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new...
Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η--cymene)Ru(pyrithionato)(pta)]PF contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs. The pta ligand was replaced by a selection of phosphine, phosphite, and arsine ligands to identify new functionalities, leading to improvement in inhibitory potency towards enzyme glutathione -transferase. In addition, cytotoxicity in breast, bone, and colon cancers was investigated.
Topics: Ruthenium; Ruthenium Compounds; Phosphines; Antineoplastic Agents; Organometallic Compounds; Coordination Complexes; Cell Line, Tumor
PubMed: 36985471
DOI: 10.3390/molecules28062499 -
Scientific Reports Feb 2019Engineered small molecule triggers are important tools for the control and investigation of biological processes, in particular protein function. Staudinger reductions...
Engineered small molecule triggers are important tools for the control and investigation of biological processes, in particular protein function. Staudinger reductions of aryl azides to amines through the use of phosphines can trigger an elimination reaction, and thereby activation of a functional molecule, if an appropriately positioned leaving group is present. We conducted detailed investigations of the effect of aryl azide and phosphine structure on both the mechanism and kinetics of these reaction-induced eliminations and identified phosphine/azide pairs that enable complete activation within minutes under physiologically relevant conditions.
Topics: Azides; Chromatography, Liquid; Kinetics; Mass Spectrometry; Molecular Structure; Phosphines; Small Molecule Libraries
PubMed: 30728367
DOI: 10.1038/s41598-018-37023-6 -
Journal of the American Chemical Society Apr 2016The ability to regulate small molecule chemistry in vivo will enable new avenues of exploration in imaging and pharmacology. However, realization of these goals will...
The ability to regulate small molecule chemistry in vivo will enable new avenues of exploration in imaging and pharmacology. However, realization of these goals will require reactions with high specificity and precise control. Here we demonstrate photocontrol over the highly specific Staudinger-Bertozzi ligation in vitro and in vivo. Our simple approach, photocaging the key phosphine atom, allows for the facile production of reagents with photochemistry that can be engineered for specific applications. The resulting compounds, which are both stable and efficiently activated, enable the spatial labeling of metabolically introduced azides in vitro and on live zebrafish.
Topics: Animals; Azides; Embryo, Nonmammalian; Fluoresceins; HEK293 Cells; Hexosamines; Humans; Microscopy, Fluorescence; Molecular Imaging; Phosphines; Photochemistry; Ultraviolet Rays; Zebrafish
PubMed: 27010217
DOI: 10.1021/jacs.5b13401 -
ACS Applied Materials & Interfaces Feb 2020Design and synthesis of nanostructured responsive gels have attracted increasing attention, particularly in the biomedical domain. Polymer chain configurations and...
Design and synthesis of nanostructured responsive gels have attracted increasing attention, particularly in the biomedical domain. Polymer chain configurations and nanodomain sizes within the network can be used to steer their functions as drug carriers. Here, a catalyst-free facile one-step synthesis strategy is reported for the design of pH-responsive gels and controlled structures in nanoscale. Transparent and impurity free gels were directly synthesized from trivinylphosphine oxide (TVPO) and cyclic secondary diamine monomers via Michael addition polymerization under mild conditions. NMR analysis confirmed the consumption of all TVPO and the absence of side products, thereby eliminating post purification steps. The small-angle X-ray scattering (SAXS) elucidates the nanoscale structural features in gels, that is, it demonstrates the presence of collapsed nanodomains within gel networks and it was possible to tune the size of these domains by varying the amine monomers and the nature of the solvent. The fabricated gels demonstrate structure tunability via solvent-polymer interactions and pH specific drug release behavior. Three different anionic dyes (acid blue 80, acid blue 90, and fluorescein) of varying size and chemistry were incorporated into the hydrogel as model drugs and their release behavior was studied. Compared to acidic pH, a higher and faster release of acid blue 80 and fluorescein was observed at pH 10, possibly because of their increased solubility in alkaline pH. In addition, their release in phosphate buffered saline (PBS) and simulated body fluid (SBF) matrix was positively influenced by the ionic interaction with positively charged metal ions. In the case of hydrogel containing acid blue 90 a very low drug release (<1%) was observed, which is due to the reaction of its accessible free amino group with the vinyl groups of the TVPO. In vitro evaluation of the prepared hydrogel using human dermal fibroblasts indicates no cytotoxic effects, warranting further research for biomedical applications. Our strategy of such gel synthesis lays the basis for the design of other gel-based functional materials.
Topics: Drug Carriers; Drug Liberation; Gels; Hydrogels; Hydrogen-Ion Concentration; Oxides; Phosphines; Polymerization; Scattering, Small Angle
PubMed: 31972075
DOI: 10.1021/acsami.9b22808 -
PloS One 2018The red palm weevil Rhynchophorus ferrugineus (Olivier) is an important pest of date palms in many regions of the world. This paper reports the first survey of...
The red palm weevil Rhynchophorus ferrugineus (Olivier) is an important pest of date palms in many regions of the world. This paper reports the first survey of insecticide resistance in field populations of R. ferrugineus in Pakistan which were collected from seven date palm growing areas across Punjab and Khyber Pakhtunkhwa (KPK) provinces, Pakistan. The resistance was assessed by the diet incorporation method against the formulated commonly used chemical insecticides profenophos, imidacloprid, chlorpyrifos, cypermethrin, deltamethrin, spinosad, lambda-cyhalothrin and a fumigant phosphine. Elevated levels of resistance were recorded for cypermethrin, deltamethrin and phosphine after a long history of insecticide use in Pakistan. Resistance Ratios (RRs) were 63- to 79-fold for phosphine, 16- to 74-fold for cypermethrin, 13- to 58-fold for deltamethrin, 2.6- to 44-fold for profenophos, 3- to 24-fold for chlorpyrifos, 2- to 12-fold for lambda-cyhalothrin and 1- to 10-fold for spinosad compared to a susceptible control line. Resistant R. ferrugineus populations were mainly found in southern Punjab and to some extent in KPK. The populations from Bahawalpur, Vehari, Layyah and Dera Ghazi Khan were most resistant to chemical insecticides, while all populations exhibited high levels of resistance to phosphine. Of the eight agents tested, lower LC50 and LC90 values were recorded for spinosad and lambda-cyhalothrin. These results suggest that spinosad and lambda-cyhalothrin exhibit unique modes of action and given their better environmental profile, these two insecticides could be used in insecticide rotation or assist in phasing out the use of older insecticides. A changed pattern of both insecticides can be used sensibly be recommended without evidence of dose rates and frequencies used.
Topics: Animals; Chlorpyrifos; Drug Combinations; Inhibitory Concentration 50; Insecticide Resistance; Insecticides; Macrolides; Neonicotinoids; Nitriles; Nitro Compounds; Organothiophosphates; Pakistan; Phoeniceae; Phosphines; Plant Diseases; Pyrethrins; Weevils
PubMed: 30024882
DOI: 10.1371/journal.pone.0192628 -
Journal of the American Chemical Society Feb 2021The development of fluorescent dyes that emit and absorb light at wavelengths greater than 700 nm and that respond to biochemical and biophysical events in living...
The development of fluorescent dyes that emit and absorb light at wavelengths greater than 700 nm and that respond to biochemical and biophysical events in living systems remains an outstanding challenge for noninvasive optical imaging. Here, we report the design, synthesis, and application of near-infrared (NIR)-absorbing and -emitting optical voltmeter based on a sulfonated, phosphine-oxide (po) rhodamine for voltage imaging in intact retinas. We find that po-rhodamine based voltage reporters, or poRhoVRs, display NIR excitation and emission profiles at greater than 700 nm, show a range of voltage sensitivities (13 to 43% ΔF/F per 100 mV in HEK cells), and can be combined with existing optical sensors, like Ca-sensitive fluorescent proteins (GCaMP), and actuators, like light-activated opsins ChannelRhodopsin-2 (ChR2). Simultaneous voltage and Ca imaging reveals differences in activity dynamics in rat hippocampal neurons, and pairing poRhoVR with blue-light based ChR2 affords all-optical electrophysiology. In retinas isolated from a mouse model of retinal degeneration, poRhoVR, together with GCaMP-based Ca imaging and traditional multielectrode array (MEA) recording, can provide a comprehensive physiological activity profile of neuronal activity, revealing differences in voltage and Ca dynamics within hyperactive networks of the mouse retina. Taken together, these experiments establish that poRhoVR will open new horizons in optical interrogation of cellular and neuronal physiology in intact systems.
Topics: Animals; Calcium; Fluorescent Dyes; Infrared Rays; Mice; Neurons; Optical Imaging; Oxides; Phosphines; Retina; Rhodamines
PubMed: 33501825
DOI: 10.1021/jacs.0c11382 -
Environmental Health Perspectives Sep 2005
Topics: Air Pollution, Indoor; Ammonia; Drug Compounding; Hazardous Substances; Humans; Hydrochloric Acid; Illicit Drugs; Inhalation Exposure; Methamphetamine; Phosphines; Waste Management
PubMed: 16158522
DOI: 10.1289/ehp.113-a589a -
Scientific Reports Mar 2023Phosphine (PH) and ethyl formate (EF), the two popular fumigant disinfectants of stored product insect pests, are primarily evaluated for their knock down effects...
Phosphine (PH) and ethyl formate (EF), the two popular fumigant disinfectants of stored product insect pests, are primarily evaluated for their knock down effects without considering their post-fumigation sub-lethal activities. The sub-lethal activities (adult survivorship, fecundity, sterility and female sex pheromone production) of the fumigants were evaluated on a field-to-storage insect pest adzuki bean beetle, Callosobruchus chinensis (L.). The adults' survivorship and female fecundity, both were dose-dependently affected by sub-lethal PH and EF fumigation exposures. Hatchability of the eggs laid by fumigated female adults were also significantly affected. Gas-chromatography mass-spectrometry analysis of solid-phase micro-extraction from virgin fumigated C. cinensis females revealed that the PH LC (the lethal concentration required to kill the 25% of the population) fumigated female C. chinensis released significantly less amount of the pheromone components. In contrast, EF LC exposure did not affect the pheromone release. This study unveils the facts that the EF and PH fumigation have detrimental bioactivities against C. chinensis. Notably, this suggests to consider the sub-lethal EF and PH fumigation rather than the dose required to instantly kill all the C. chinensis individuals for disinfestation of stored adzuki bean.
Topics: Female; Animals; Sex Attractants; Pheromones; Survivorship; Fumigation; Coleoptera; Insecta; Phosphines; Fertility; Insecticides
PubMed: 36922539
DOI: 10.1038/s41598-023-30190-1