Usefulness of A Model-Based Approach for Estimating In Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay

Aim: Enamino 3-benzazecine compounds, incorporating the C6-C8 allene system, were synthesized and evaluated in vitro as inhibitors of P-glycoprotein (P-gp) and/or multidrug resistance-associated protein 1 (MRP1), two efflux pumps mainly connected with multidrug resistance (MDR) in cancer cells. Results & methodology: Most of the synthesized compounds were selective P-gp inhibitors in Calcein-AM uptake assay. Structure–activity relationships (SARs) pointed out that CO2Me derivatives are more potent than acetyl derivatives, and 10,11-dimethoxy compounds are five to tenfold more potent inhibitors than the respective unsubstituted compounds, and that the P-gp inhibition potency is mainly related to volume parameters. Conclusion: Nanomolar P-gp inhibitors, such as 23 (IC50 = 4.2 nM), restored the antiproliferative activity of doxorubicin in multidrug-resistant cells. The observed activities showed that 3-benzazecine-based compounds may be promising MDR reversers.

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Faculty Opinions recommendation of Variability in P-glycoprotein inhibitory potency (IC₅₀) using various in vitro experimental systems: implications for universal digoxin drug-drug interaction risk assessment decision criteria.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718043074.793480891 ◽

2013 ◽

Author(s):

Bruno Stieger

Keyword(s):

Risk Assessment ◽

Drug Interaction ◽

Decision Criteria ◽

Inhibitory Potency ◽

Experimental Systems ◽

P Glycoprotein ◽

Drug Drug Interaction

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Synthesis and DFT Study on Hantzsch Reaction to Produce Asymmetrical Compounds of 1,4-Dihydropyridine Derivatives for P-Glycoprotein Inhibition as Anticancer Agent

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892813666180220112613 ◽

2018 ◽

Vol 13 (2) ◽

pp. 255-264 ◽

Cited By ~ 6

Author(s):

Shirin Mollazadeh ◽

Fatemeh Moosavi ◽

Farzin Hadizadeh ◽

Mahmoud Seifi ◽

Javad Behravan ◽

...

Keyword(s):

Anticancer Agent ◽

Dft Study ◽

Hantzsch Reaction ◽

P Glycoprotein ◽

Glycoprotein Inhibition ◽

Dihydropyridine Derivatives

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Smells Like Teen Spirit—A Model to Generate Laundry-Associated Malodour In Vitro

Microorganisms ◽

10.3390/microorganisms9050974 ◽

2021 ◽

Vol 9 (5) ◽

pp. 974

Author(s):

Marc-Kevin Zinn ◽

Marco Singer ◽

Dirk Bockmühl

Keyword(s):

Volatile Compounds ◽

Micrococcus Luteus ◽

Dimethyl Disulfide ◽

Bacterial Strains ◽

Dimethyl Trisulfide ◽

Model Based ◽

Washing Machines ◽

Staphylococcus Hominis

Although malodour formation on textiles and in washing machines has been reported to be a very relevant problem in domestic laundry, the processes leading to bad odours have not been studied intensively. In particular, the smell often described as “wet-and-dirty-dustcloth-like malodour” had not been reproduced previously. We developed a lab model based on a bacterial mixture of Micrococcus luteus, Staphylococcus hominis, and Corynebacterium jeikeium, which can produce this odour type and which might allow the detailed investigation of this problem and the development of counteractions. The model uses bacterial strains that have been isolated from malodourous textiles. We could also show that the three volatile compounds dimethyl disulfide, dimethyl trisulfide, and indole contribute considerably to the “wet-fabric-like” malodour. These substances were not only found to be formed in the malodour model but have already been identified in the literature as relevant malodourous substances.

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