Design of Novel 2-Phenylquinazolin-4-amines as Selective CYP1B1 Inhibitors for Overcoming Paclitaxel Resistance in A549 Cells.

Cytochrome P450 1B1 (CYP1B1) contributes to the metabolic inactivation of chemotherapeutics when overexpressed in tumor cells. Selective inhibition of CYP1B1 holds promise for reversing drug resistance. In our pursuit of potent CYP1B1 inhibitors, we designed and synthesized a series of 2-phenylquinazolin-4-amines.

Design, Synthesis, and Evaluation of F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin.

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC determinations, most of these probes exhibited good affinity and selectivity to CYP1B1.

Development of [F]Thiazolylacylaminopyridine-Based Glycogen synthase Kinase-3β ligands for positron emission tomography imaging.

Glycogen synthase kinase-3β (GSK-3β) regulates numerous of CNS-specific signaling pathways, and is particularly implicated in various pathogenetic mechanisms of Alzheimer's disease (AD). A noninvasive method for detecting GSK-3β in AD brains via positron emission tomography (PET) imaging could enhance the understanding of AD pathogenesis and aid in the development of AD therapeutic drugs. In this study, an array of fluorinated thiazolyl acylaminopyridines (FTAAP) targeting GSK-3β were designed and synthesized.

Gas-phase formation of Grignard-type organolanthanide (III) ions RLnCl : The influences of lanthanide center and hydrocarbyl group.

Rationale: Compared with organomagnesium compounds (Grignard reagents), the Grignard-type organolanthanides (III) exhibit several utilizable differences in reactivity. However, the fundamental understanding of Grignard-type organolanthanides (III) is still in its infancy. Decarboxylation of metal carboxylate ions is an effective method to obtain organometallic ions that are well suited for gas-phase investigation using electrospray ionization (ESI) mass spectrometry in combination with density functional theory (DFT) calculations.

Dual-Ligand Strategy for the Preparation of Gas-Phase Uranyl(VI) Benzyne Complexes from Uranyl(VI) Benzoates.

The uranyl(VI) benzyne complex (η-CH)UOCl was prepared in the gas phase by electrospray ionization mass spectrometry coupled with collision-induced dissociation. It was formed via a dual-ligand strategy that requires the elimination of benzoic acid or benzene/CO from the uranyl dibenzoate precursor (CHCO)UOCl. This contrasts the known strategy for the formation of gas-phase benzyne complexes that would result from CO/HCl elimination from (CHCO)UOCl, during which only one benzoate ligand is involved.

A new class of CYP1B1 inhibitors derived from bentranil.

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines.

Gas-phase synthesis and structure of thorium benzyne complexes.

The thorium benzyne complex (η-CH)ThCl was synthesized in the gas phase through consecutive decarboxylation and dehydrochlorination from the (CHCO)ThCl precursor upon collision-induced dissociation. Theoretical calculations suggest that (η-CH)ThCl exhibits a metallacyclopropene structure with two polarized Th-C σ bonds. This procedure can be generally extended to the synthesis of a wide range of gas-phase thorium benzyne complexes.

Discrimination and quantitation of halobenzoic acid positional isomers upon Th(IV) coordination by mass spectrometry.

A fast and reliable mass spectrometry-based method has been developed to discriminate the positional isomers of -, - and -CHXCOH (X = F, Cl and Br). This is based on the distinct fragmentation patterns of isomeric ThCl(CHXCO) ions generated by electrospray ionization of the solutions with CHXCOH isomers and ThCl. Moreover, the composition of these positional isomers can be conveniently quantified without any pre-treatment according to the proportion of gas-phase fragmentation products.

Preparation of a bifunctional pyrazosulfuron-ethyl imprinted polymer with hydrophilic external layers by reversible addition-fragmentation chain transfer polymerization and its application in the sulfonylurea residue analysis.

A new bifunctional pyrazosulfuron-ethyl imprinted polymer was synthesized by the combination of molecular imprinting technology and living radical polymerization. In the synthesis, the pyrazosulfuron-ethyl imprinted polymer was obtained by the reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization followed by grafting poly(glyceryl monomethacrylate) (pGMMA) by the post-RAFT polymerization. In this research, we used polyethylene glycol (PEG) as the polymeric porogen in order to increase the porosity of the material which is a new porogen application in the precipitation polymerization.