4-(4-(Methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one: a novel COX-2 inhibitor acting selectively and directly on cancerous B-lymphocyte mitochondria

A new series of 3-phenoxyazetidin-2-ones (β-lactams) were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In this study, the effects of a synthetic of β-lactam-structured COX-2 inhibitor with 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one on cell viability of cancerous lymphoblast isolated from patients diagnosed with acute lymphocytic leukemia (ALL) and normal lymphocytes collected from healthy donors were investigated. The viability % of cancer lymphoblast and normal lymphocyte treated 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one were tested with MTT assay. Apoptosis and necrosis were measured by double stains of annexin V and propidium iodide, and caspase-3 as a final mediator in apoptotic death measured by colorimetric assay. Mitochondria were isolated from both cancerous lymphoblast and normal lymphocytes to measure parameters of mitochondrial damage such as reactive oxygen species (ROS) formation, mitochondrial membrane potential decrease, swelling, and cytochrome c release following the administration of azithidine-2-one derivative, 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one. Our results showed that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one inhibited proliferation of cancerous lymphoblast in a concentration-dependent manner by inducing apoptosis but not in normal lymphocytes. Treatment with azithidine-2-one derivative produced a rapid loss of mitochondrial transmembrane potential, stimulation of release of ROS and mitochondrial cytochrome c into cytosol, and subsequent induction of procaspase-9 processing. Data suggest that 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one-induced ROS production led to mitochondria-mediated death signaling that resulted in apoptosis in cancerous lymphoblast cells. The induction of apoptosis by azithidine-2-one compounds, such as 4-(4-(methylsulfonyl)phenyl)-3-phenoxy-1-phenylazetidin-2-one, may provide a mechanism for its cancer chemopreventive action in acute lymphocytic leukemia cells.     

Portland cement solidified construction waste using MSW leachate and phosphate admixtures

Journal of Material Cycles and Waste Management - Many dumping sites all over the world release leachate into the environment. The primary goal of this study was to convert raw municipal...     

Spatial and temporal distributions of air pollutant emissions from open crop straw and biomass burnings in China from 2002 to 2016

Environmental Chemistry Letters - Open biomass burning (OBB) with a main contribution from open crop straw burning (OCSB) plays a key role in the formation of heavy haze episodes during harvest...     

Residential emissions predicted as a major source of fine particulate matter in winter over the Yangtze River Delta,China

Environmental Chemistry Letters - Air pollution is an increasingly critical health issue responsible for numerous diseases and deaths worldwide. In China, to address severe air pollution in the...     

Introduction of Ionic Liquids as Highly Efficient Plasticizers and Flame Retardants of Cellulose Triacetate Films

Journal of Polymers and the Environment - As a promising biodegradable polymer, cellulose triacetate (CTA) was synthesized and plasticized with ionic liquids to produce flexible biocomposite films...     

Correction to: Role of casting and curing conditions on the strength and drying shrinkage of greener concrete

Environmental Science and Pollution Research -     

COVID-19 pandemic: impacts on bees,beekeeping, and potential role of bee products as antiviral agents and immune enhancers

Environmental Science and Pollution Research - COVID-19 pandemic has passed to the front all the contradictions of the beekeeping sector: the valuable role of bee products as immune enhancers and...     

Fuzzy-based adaptive learning network using search and rescue optimization for e-waste management model: case study

Environmental Science and Pollution Research - In recent days, the expansion of e-waste disposal should be increased due to environmental hazards, contamination of groundwater, an unconcerned...     

Application of polysaccharide-based biopolymers as supports in photocatalytic treatment of water and wastewater: a review

Environmental Chemistry Letters - Rising health issues of Worldwide pollution by fossil fuel products are Fostering the development of safer materials such as biopolymers in many sectors such as...     

Study on the kinetics of the conversion of Moroccan phosphogypsum into X2SO4 (X = Na,NH4)

Journal of Material Cycles and Waste Management - Phosphoric acid production industries use the wet process, which leads to enormous quantities of phosphogypsum (PG) as a byproduct. The discharge...