Design and Synthesis of Novel Near-Infrared Fluorescence Probes Based on an Open Conformation of a Cytochrome P450 1B1 Complex for Molecular Imaging of Colorectal Tumors

Chen, Dongmei; Li, Ruining; Shao, Qi; Wu, Zhihao; Cui, Jiahua; Meng, Qingqing; Li, Shaoshun

doi:10.1021/acs.jmedchem.3c01474

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…CYP1B1 is not only a potential target for tumor treatment but also a target for diagnosis. , As shown in Table , compounds 5l , 13a , 13b , and 13e showed strong inhibition efficiency and selectivity to CYP1B1 enzyme like their hydrochlorides. The IC 50 values were calculated according to the curves shown in Figures S10–S13.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, Li and collaborators expanded their research to include the development of near-infrared fluorescent probes that specifically target CYP1B1 and enable the detection of colorectal cancer xenografts in mice. , In 2017, Chaudhuri reported the synthesis of CYP1B1 inhibiting quinazoline, with compound 1b exhibiting robust inhibition and high selectivity for CYP1B1 . In a recent breakthrough in 2022, Zhang and collaborators reported the discovery of N -aryl-2,4-bithiazole-2-amine ( 1c ) as a potent and specific CYP1B1 inhibitor, which was capable of successfully reversing paclitaxel resistance in A549 cells .…”

Section: Introductionmentioning

confidence: 99%

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

Yang,

Huang

et al. 2024

J. Med. Chem.

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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. A substantial proportion of these newly developed inhibitors demonstrated inhibitory activity against CYP1B1, accompanied by improved water solubility. Remarkably, compound 14b exhibited exceptional inhibitory efficacy and selectivity toward CYP1B1. Molecular docking studies suggested that the expansion of the π-system through aromatization, the introduction of an amine group, and iodine atom augmented the binding affinity. Furthermore, inhibitors 14a, 14b, and 14e demonstrated the ability to significantly reduce the resistance in A549 cells to paclitaxel, while also inhibiting the migration and invasion of these cells. Finally, radioiodine labeling experiments shed light on the metabolic pathway of compound 5l in mice, highlighting the potential of 125I-5l as a radioactive probe for future research endeavors.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yang,

Huang

et al. 2024

J. Med. Chem.

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“…It should be noted that various organic systems have been studied with characteristics similar to these "wires". For example, organic fluorophores have been tethered to binding groups for P450 cam [66][67][68] and CYP1B1 [69], including a system with a pendant metal chelating group [70].…”

Section: Binding Of Metal-containing "Wires" With P450 Proteinsmentioning

confidence: 99%

The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition

Havrylyuk,

Heidary,

Glazer

2024

Biomolecules

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While cytochrome P450 (CYP; P450) enzymes are commonly associated with the metabolism of organic xenobiotics and drugs or the biosynthesis of organic signaling molecules, they are also impacted by a variety of inorganic species. Metallic nanoparticles, clusters, ions, and complexes can alter CYP expression, modify enzyme interactions with reductase partners, and serve as direct inhibitors. This commonly overlooked topic is reviewed here, with an emphasis on understanding the structural and physiochemical basis for these interactions. Intriguingly, while both organometallic and coordination compounds can act as potent CYP inhibitors, there is little evidence for the metabolism of inorganic compounds by CYPs, suggesting a potential alternative approach to evading issues associated with rapid modification and elimination of medically useful compounds.

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Pathological and pharmacological functions of the metabolites of polyunsaturated fatty acids mediated by cyclooxygenases, lipoxygenases, and cytochrome P450s in cancers

Meng,

Liu

2024

Pharmacology & Therapeutics

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Design and Synthesis of Novel Near-Infrared Fluorescence Probes Based on an Open Conformation of a Cytochrome P450 1B1 Complex for Molecular Imaging of Colorectal Tumors

Cited by 3 publications

References 45 publications

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

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

The Impact of Inorganic Systems and Photoactive Metal Compounds on Cytochrome P450 Enzymes and Metabolism: From Induction to Inhibition

Pathological and pharmacological functions of the metabolites of polyunsaturated fatty acids mediated by cyclooxygenases, lipoxygenases, and cytochrome P450s in cancers

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