Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders, 2020, Rao et al

Andy · Mar 13, 2020

Highlights
• 40 novel novel β-indoloquinazoline analogues were designed and synthesized.
• The lipid-lowering activity was evaluated based on 3T3-L1 adipocyte model.
• Compound IQZ23 shows a good drug-like properties and effectiveness on obesity mice.
• Compound IQZ23 activates AMPK pathway by modulating ATP synthase activity.
Abstract
Discovery of novel anti-obesity agents is a challenging and promising research area. Based on our previous works, we synthesized 40 novel β-indoloquinazoline analogues by altering the skeleton and introducing preferential side chains, evaluated their lipid-lowering activity and summarized the structure-activity relationships. In combination with an evaluation of the lipid-lowering efficacies, AMP-dependent activated protein kinase (AMPK) activating ability and liver microsomal stability, compound 23 (named as IQZ23) was selected for further studies. IQZ23 exerted a high efficacy in decreasing the triglyceride level (EC50 = 0.033 μM) in 3T3-L1 adipocytes. Mechanistic studies revealed the lipid-lowering activity of IQZ23 was dependent on the AMPK pathway by modulating ATP synthase activity. This activation was accompanied by mitochondrial biogenesis and oxidation capacity increased, and insulin sensitivity enhanced in pertinent cell models by various interventions. Correspondingly, IQZ23 (20 mg/kg, i.p.) treatment significantly reversed high fat and cholesterol diet (HFC)- induced body weight increases and accompanying clinical symptoms of obesity in mice but without indicative toxicity. These results indicate that IQZ23 could be a useful candidate for the treatment of obesity and related metabolic disorders.
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Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0223523420301392
Sci hub, https://sci-hub.se/10.1016/j.ejmech.2020.112172

alktipping · Mar 14, 2020

the search for profitable wonder drugs goes on . they create these thing without any real understanding of the complexity of the human body of course by the time proof of harms come about they have already pocketed the profits . imagine if all the funds were actually spent on finding out everything we do not yet know or understand about our own biology .

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Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders, 2020, Rao et al

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Discovery of a promising agent IQZ23 for the treatment of obesity and related metabolic disorders, 2020, Rao et al

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