Synthesis and Anti-Cancer Activity In Vitro of Synephrine Derivatives.

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Glucocorticoids (GCs) are standard treatments for hematological malignancies but cause adverse effects.
• Selective glucocorticoid receptor agonists (SEGRAs) offer a potential alternative with fewer side effects.
• No SEGRAs have reached clinical trials for anti-cancer applications.

Purpose of the Study:

• To synthesize and characterize novel synephrine derivatives as potential SEGRAs.
• To evaluate the in vitro anti-cancer activity of these compounds.
• To assess their binding affinity to the glucocorticoid receptor (GR) using molecular docking.

Main Methods:

• Synthesis of 26 novel synephrine derivatives.
• Characterization using HRMS, 1H, and 13C NMR.
• In vitro anti-cancer evaluation in K562 and Granta cells via MTT assay.
• In silico molecular docking to predict GR affinity.

Main Results:

• Compound 10S-E2 exhibited the highest GR affinity in silico and significant cytotoxic activity against K562 and Granta cells at ~13 µM.
• Compound 13S-G2 also showed GR affinity and cytotoxicity at 50-70 µM.
• Correlation observed between in silico GR affinity and in vitro anti-cancer efficacy.

Conclusions:

• Synephrine derivatives represent a promising class of compounds for developing novel SEGRAs.
• These derivatives demonstrate potential for anti-cancer activity in hematological malignancies.
• Further investigation is warranted to advance these compounds as potential therapeutics.