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

AbstractStilbene 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 theO-alkylation reaction and characterized using FTIR,1H NMR,13C NMR, DEPT-135, and HRMS (ESI+) spectral analysis. An MTT assay was used to test the synthesized hybrids against breast cancer (MCF-7 andT47D) and liver cancer (HepG2) cell lines. The results showed that the synthesis of coumarin-stilbene hybrids via theO-alkylation reaction requires the presence of KI in addition to K2CO3 as a base to complete the reaction. On the other hand, the synthesis of coumarin-pterostilbene hybrids (3a-b) via theO-alkylation reaction with DMF as a solvent and an excess of base (K2CO3) 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, compounds4a and4b exhibited the best cytotoxic activity againstT47D andMCF-7, with IC50 values of 102.05 and 23.12  µM, respectively. Co...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research