Structure-activity relationship and molecular mechanisms of ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4h-chromene-3-carboxylate (sha 14-1) and its analogues.

doi:10.1021/jm9005059

Paper

Structure-activity relationship and molecular mechanisms of ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4h-chromene-3-carboxylate (sha 14-1) and its analogues.

Published Sep 10, 2009 · S. Das, Jignesh M. Doshi, Defeng Tian

Journal of medicinal chemistry

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65

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1

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Abstract

Rapid development of multiple drug resistance against current therapies is a major barrier in the treatment of cancer. Therefore, anticancer agents that can overcome acquired drug resistance in cancer cells are of great importance. Previously, we have demonstrated that ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4H-chromene-3-carboxylate (5a, sHA 14-1), a stable analogue of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (6, HA 14-1), mitigates drug resistance and synergizes with a variety of cancer therapies in leukemia cells. Structure-activity relationship (SAR) studies of 5a guided the development of ethyl 2-amino-6-(3',5'-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (5q, CXL017), a compound with low micromolar cytotoxicity against a wide-range of hematologic and solid tumor cells. More excitingly, our studies of 5q in camptothecin (CCRF-CEM/C2) and mitoxantrone (HL-60/MX2) resistant cancer cells highlight its ability to selectively kill drug-resistant cells over parent cancer cells. 5q inhibits tumor cell growth through the induction of apoptosis, with detailed mechanism of its selectivity toward drug-resistant cancer cells under investigation. These results suggest that 5q is a promising candidate for treatment of cancers with multiple drug resistance.

Study Snapshot

5q, a promising anticancer agent, selectively kills drug-resistant cancer cells and inhibits tumor cell growth through apoptosis, offering a promising treatment option for multiple drug-resistant cancers.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Structure-activity relationship and molecular mechanisms of ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4h-chromene-3-carboxylate (sha 14-1) and its analogues.

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References

Citations

Reappraisal of the fundamental mechanisms of the sHA14-1 molecule as a Bcl-2/Bcl-XL ligand in the context of anticancer therapy: A cell biological study

SHA14-1 plays a complex multifunctional role in cancer cells, potentially complicating its potential application as an anticancer therapy due to its more complex actions than initially intended.

Synthesis and Characterization of a New Class of Chromene-Azo Sulfonamide Hybrids as Promising Anticancer Candidates with the Exploration of Their EGFR, hCAII, and MMP-2 Inhibitors Based on Molecular Docking Assays

Chromene-Azo Sulfonamide Hybrids show promising anticancer activity and show potential as EGFR, hCAII, and MMP-2 inhibitors, outperforming Cisplatin in efficacy.

Recent advances in small molecule and peptide inhibitors of glucose-regulated protein 78 for cancer therapy.

Targeting GRP78, a key protein in cancer, shows potential as a promising therapeutic strategy for cancer therapy, but current GRP78 inhibitors have not been approved for clinical use.

Nanocomposite Fe3O4@GO-NH as a Reusable Heterogeneous Catalyst for the Three-component Synthesis of 2-Amino-4H-chromenes

Nanocomposite Fe3O4@GO-NH offers a reusable, greener catalyst for the efficient synthesis of 2-amino-4H-chromenes, with potential applications in anticancer and anti-rheumatic drug design.

Facile synthesis of pyrazole derivatives using reusable Fe3O4@MCM-41-SO3H

Fe3O4-MCM-41-SO3H is a magnetically reusable catalyst for the facile synthesis of pyrazole derivatives in high yields under solvent-free conditions and with a simple work-up process.

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SERCA inhibitors effectively suppress oncogenic Notch1 signaling without causing overt calcium overload, offering a potential alternative to -secretase modulators with limited clinical activity due to severe side effects.