Synthesis and anticancer activity of novel coumarin-stilbene hybrids with different hydrocarbon chains as linkers

• Published in: Medicinal chemistry research 2024, Vol.33 (5), p.764-778
• Main Authors: Al-lehaib, Lamya A., Ali, Ehab M. M., Al-Footy, Khalid O., El-Shishtawy, Reda M.
• Format: Article
• Language: English
• Subjects: Alkylation; Anticancer properties; Antitumor activity; Biochemistry; Biological activity; Biological effects; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cancer; Catalysts; Cisplatin; Coumarin; Cytotoxicity; Hepatocytes; Hybridization; Hybrids; Hydrocarbons; Inorganic Chemistry; Liver cancer; Medicinal Chemistry; Molecular chains; NMR; Nuclear magnetic resonance; Original Research Article; Pharmacology/Toxicology; Polyphenols; Potassium carbonate; Resveratrol; Spectrum analysis; Stilbene; Tumor cell lines
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-024-03212-4

Stilbene derivatives (pterostilbene and resveratrol) and 4-methylumbelliferone occur naturally in plants. These compounds and coumarin-stilbene hybrids have a variety of biological activities. It was envisioned that the molecular hybridization strategy would produce new bioactive molecules. Thus, six new coumarin-stilbene hybrids ( 3a-b, 4a-b, and 5a-b) with different hydrocarbon chains as linkers were synthesized by the O -alkylation reaction and characterized using FTIR, 1 H NMR, 13 C NMR, DEPT-135, and HRMS (ESI+) spectral analysis. An MTT assay was used to test the synthesized hybrids against breast cancer ( MCF-7 and T47D ) and liver cancer ( HepG2 ) cell lines. The results showed that the synthesis of coumarin-stilbene hybrids via the O -alkylation reaction requires the presence of KI in addition to K 2 CO 3 as a base to complete the reaction. On the other hand, the synthesis of coumarin-pterostilbene hybrids ( 3a-b ) via the O -alkylation reaction with DMF as a solvent and an excess of base (K 2 CO 3 ) and catalyst (KI) improved the yield significantly (65.43 and 73.71%, respectively). The biological results exhibited that all hybrids showed moderate to weak anticancer activities, much lower than the medication (cisplatin). However, most compounds showed superior activities than parent compounds against three different human cell lines. Among them, compounds 4a and 4b exhibited the best cytotoxic activity against T47D and MCF-7 , with IC 50 values of 102.05 and 23.12 µM, respectively. Compound ( 3a ) showed the most cytotoxic activity against HepG2 , with an IC 50 value of 80.09 µM. To conclude, due to the simplicity of synthesis, hybridization is a promising strategy for producing new hybrid compounds with hydrocarbon chains as linkers and improving biological activity compared with their parent compounds.