Synthesis and elucidation of strained galactopyronose esters as selective cyclooxygenase-2 inhibitor: a comprehensive computational approach.

Cyclooxygenase-2 (COX-2) is critically implicated in various pathologies, including inflammation, cancer, disorders involving the nervous system, and multidrug resistance. In both academic and pharmaceutical research, the development of COX-2 selective drugs as anti-inflammatory and anti-tumor therapeutics is a key focus. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) have ulcerogenic, gastrointestinal adverse effects, and myocardial infarction risk, which resulted in their limited applications.

A dual-function chromogenic and fluorogenic benzofurazan probe for plazomicin and its innovative utility for development of two microwell assays with high throughput for analysis of drug substance and pharmaceutical formulations.

Plazomicin (PLZ) is a novel aminoglycoside which has been recently approved by The US Food and Drug Administration for the treatment of complicated urinary tract infections including acute pyelonephritis, caused by certain Enterobacteriaceae, in adult patients with limited or no options for alternative treatment. This study focuses on the development of microwell-based photometric and fluorometric assays for the quantitative determination of PLZ in its bulk drug substance and commercial pharmaceutical formulations (Zemedri® injections). Both assays utilize the dual-function chromogenic and fluorogenic properties of the 4-fluoro-7-nitrobenzofurazan (NBD-F) probe.

-Alkylated quinazolin-4(3)-ones as dual EGFR/VEGFR-2 kinases inhibitors: design, synthesis, anticancer evaluation and docking study.

Dual targeting by a single molecule has emerged as a promising strategy for fighting cancer. In this study, a new set of 2-thioquinazolin-4(3)-ones as potential anti-cancer surrogates endowed with dual EGFR/VEGFR-2 kinases inhibitory activities were synthesized. The anti-tumor potency of the newly synthesized candidates 4-27 was evaluated against a panel of four cancer cell lines.

Discovery of new 1,3-diphenylurea appended aryl pyridine derivatives as apoptosis inducers through c-MET and VEGFR-2 inhibition: design, synthesis, and studies.

Interest has been generated in VEGFR-2 and c-MET as potential receptors for the treatment of different malignancies. Using aryl pyridine derivatives with 1,3-diphenylurea attached, a number of promising dual VEGFR-2 and c-MET inhibitors were developed and synthesized. Regarding the molecular target, compounds 2d, 2f, 2j, 2k, and 2n had potent IC values of 65, 24, 150, 170, and 18 nM against c-MET, respectively.

Synthesis, enzyme inhibition assay, and molecular modeling study of novel pyrazolines linked to 4-methylsulfonylphenyl scaffold: antitumor activity and cell cycle analysis.

Antitumor activity using 59 cancer cell lines and enzyme inhibitory activity of a newly synthesized pyrazoline-linked 4-methylsulfonylphenyl scaffold (compounds 18a-q) were measured and compared with those of standard drugs. Pyrazolines 18b, 18c, 18f, 18g, 18h, and 18n possessed significant antitumor activity, with a positive cytotoxic effect (PCE) of 22/59, 21/59, 21/59, 48/59, 51/59, and 20/59, respectively. The cancer cell lines HL60, MCF-7, and MDA-MB-231 were used to measure the IC values of derivatives 18c, 18g, and 18h the MTT assay method, and the results were compared with those of reference drugs.

Copper-Vit B MOF preparation, characterization and catalytic evaluation in a one-pot synthesis of benzoxanthenones with docking validation as anti .

Copper-Vit B MOF was successfully prepared by efficient and eco hydrothermal method. The prepared MOF was characterized as a tetragonal crystal copper-MOF nanoparticles by FTIR, SEM, TEM, EDX and XRD. The prepared nanoparticles were used as an effective, inexpensive and low-toxic catalyst in the one-pot synthesis of some new benzoxanthenone derivatives.

A novel ultrasensitive chemiluminescence enzyme immunoassay by employment of a signal enhancement of horseradish peroxidase-luminol-hydrogen peroxide reaction for the quantitation of atezolizumab, a monoclonal antibody used for cancer immunotherapy.

This study describes, for the first time, the development and validation of a novel ultrasensitive chemiluminescence enzyme immunoassay (CLEIA) for the quantification of atezolizumab (ATZ), a monoclonal antibody approved by the FDA for treatment of different types of cancer. The assay involved the non-competitive binding of ATZ to its specific antigen (PD-L1 protein). The immune complex of PD-L1/ATZ formed on the internal surface of the plate wells was quantified by a novel chemiluminescence (CL)-producing horseradish peroxidase (HRP) reaction.

Exploring HCl-HCl interactions: QZVPP calculations, improved Lennard-Jones potential, and second virial coefficient analysis for thermodynamics and industrial applications.

In this paper, we present a comprehensive analysis of HCl-HCl interactions, including QZVPP calculations, energy fitting, conformation validation, and the determination of the second virial coefficient using improved Lennard-Jones (ILJ) potential parameters. To acquire accurate interaction energies, initial QZVPP calculations are performed on approximately 1851 randomly generated HCl-HCl conformations. Then, these energies are used to fit an improved Lennard-Jones potential energy surface, allowing for a robust description of HCl-HCl interactions.

Development of two highly sensitive and selective sensor-assisted fluorescence immunoassays for trace determination of copper residues in food samples.

This study describes the development of two highly sensitive and selective sensor-assisted fluorescence immunoassays for the trace determination of copper ions, Cu(ii) residues, in food samples. These assays were the microwell-based fluoroimmuoassay (FIA) and the kinetic exclusion assay (KinExA). FIA and KinExA were assisted by a microplate reader and a KinExA™ 3200 immunosensor, respectively.

Synthesis of a novel hydrazone-based compound applied as a fluorescence turn-on chemosensor for iron(iii) and a colorimetric sensor for copper(ii) with antimicrobial, DFT and molecular docking studies.

Hydrazone-hydrazide-based linkers perform a crucial role in environmental as well as biological fields. Such linkers are employed to detect exact metal ions at a minute level; hence, numerous probes are available. Even though thiophene-based molecules have a unique position in the medicinal arena, only very few chemosensors are reported based on such a moiety.

Development and validation of an UPLC-ESI-MS/MS method for quantification of duvelisib in plasma: application to pharmacokinetic study in rats.

Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It is used for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This study describes the development and validation of a new highly sensitive and efficient UPLC-ESI-MS/MS method for quantitation of DUV in plasma samples and its application to the pharmacokinetic study of DUV in rats.

Profiling of , and reactive zorifertinib metabolites using liquid chromatography ion trap mass spectrometry.

Zorifertinib (AZD-3759; ZFB) is a potent, novel, oral, small molecule used for the treatment of non-small cell lung cancer (NSCLC). ZFB is Epidermal Growth Factor Receptor (EGFR) inhibitor that is characterized by good permeability of the blood-brain barrier for (NSCLC) patients with EGFR mutations. The present research reports the profiling of , and reactive metabolites of ZFB.

Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a contagious respiratory tract infection that has become a global burden since the end of 2019. Notably, fewer patients infected with SARS-CoV-2 progress from acute disease onset to death compared with the progression rate associated with two other coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Several research organizations and pharmaceutical industries have attempted to develop successful vaccine candidates for the prevention of COVID-19.

Correction: and metabolism of ribociclib: a mass spectrometric approach to bioactivation pathway elucidation and metabolite profiling.

[This corrects the article DOI: 10.1039/D0RA01624A.].

and metabolism of ribociclib: a mass spectrometric approach to bioactivation pathway elucidation and metabolite profiling.

Ribociclib (RBC, Kisqali®) is a highly selective CDK4/6 inhibitor that has been approved for breast cancer therapy. Initially, prediction of susceptible sites of metabolism and reactivity pathways were performed by the StarDrop WhichP450™ module and the Xenosite web predictor tool, respectively. Later, metabolites and adducts of RBC were characterized from rat liver microsomes using LC-MS/MS.

Identification and characterization of , , , and reactive metabolites of infigratinib using LC-ITMS: bioactivation pathway elucidation and toxicity studies of its metabolites.

Infigratinib (INF) is a novel, small molecule that is orally administered to inhibit human fibroblast growth factor receptors (FGFRs), which are a family of receptor tyrosine kinases that may be upregulated in different tumor cell types. On 6 January 2020, the FDA granted fast track designation to INF for first-line treatment of cholangiocarcinoma. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) for INF was performed by the Xenosite web predictor tool.

Ecofriendly densitometric RP-HPTLC method for determination of rivaroxaban in nanoparticle formulations using green solvents.

A literature survey revealed no suitable "reversed phase-high performance thin layer chromatography (RP-HPTLC)" method for the analysis of rivaroxaban in nanoparticle (NP) formulations. Therefore, a novel rapid, simple, economical and environment friendly RP-HPTLC method has been established for the quantification of rivaroxaban in NP formulations and commercial tablets. RP-HPTLC analysis of rivaroxaban was performed using "RP-18 silica gel 60 F254S HPTLC plates".

Sapitinib: reactive intermediates and bioactivation pathways characterized by LC-MS/MS.

Sapitinib (AZD8931, SAP) is an epidermal growth factor receptor (EGFR) family (pan-erbB) tyrosine kinase inhibitor. In multiple tumor cell lines, SAP has been shown to be a much more potent inhibitor of EGF-driven cellular proliferation than gefitinib. In this metabolic study, we tested the generation of reactive intermediates from SAP using human liver microsomes and a capturing agent (potassium cyanide) to trap the iminium reactive intermediates.

Validated liquid chromatography tandem mass spectrometry for simultaneous quantification of foretinib and lapatinib, and application to metabolic stability investigation.

Foretinib (GSK1363089, FTB) is a multikinase inhibitor that inhibits multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor-2 and mesenchymal-epithelial transition factor, with the potential for solid tumor treatment. Lapatinib (LPB) is a significant promising drug molecule that was approved by the USFDA and was utilized to develop a nontoxic and very efficient targeted therapy against breast cancer. There is an ongoing clinical trial for using of FTB and LPB combination for HER-2 positive metastatic breast cancer treatment.

Reactive intermediates in copanlisib metabolism identified by LC-MS/MS: phase I metabolic profiling.

Copanlisib (CNB; Aliqopa™) is a novel, intravenous phosphoinositide 3-kinase inhibitor used to treat various solid and hematological malignancies. CNB was recently approved by the U.S.

Characterization of reactive intermediates formation in dacomitinib metabolism and bioactivation pathways elucidation by LC-MS/MS: phase I metabolic investigation.

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs. In the current study, metabolites of phase I for DCB were systematically explored. DCB reactive metabolites were also investigated in rat liver microsomes in presence of potassium cyanide or methoxylamine that were employed as capturing agents for iminium reactive intermediates and aldehyde, respectively, to form stable complexes which can be detected by LC-MS/MS.

Substituted spirooxindole derivatives as potent anticancer agents through inhibition of phosphodiesterase 1.

Spirooxindole is a promising chemo therapeutic agent. Possible targets include cancers of the liver, prostate, lung, stomach, colon, and breast. Here, we demonstrate a one-pot three-component reaction a [3 + 2] cycloaddition/ring contraction sequence of a dipolarophile (activated alkene) with -generated azomethine ylide (1,3-dipoles) without the use of any catalyst.