INTRODUCTION: Multiple Myeloma (MM) is a disorder characterized by accumulation of malignant plasma cells in the bone marrow microenvironment with elevated levels of abnormal monoclonal proteins (M-proteins) in the blood. These M-proteins offer no beneficial effect but crowding out normal functioning antibodies and preventing them from fighting infection. It is estimated that there will be 34,470 cases in 2022 with the overall 5-year survival rate of 54%. Caffeic acid phenethyl ester (CAPE) is reported to have a plethora of bioactive properties including antitumor traits. We previously reported that CAPE inhibits growth of MM cell growth through induction of apoptosis and oxidative stress. Objective of this study is to evaluate the effects of novel CAPE derivatives on human MM cell growth. METHODS: CAPE derivatives were synthesized by coupling the caffeic acid with derivatives of phenylalanine and tyrosine. Cultured MM cells were exposed to CAPE and its derivatives (0 ~ 50μM) for 24, 48, or 72 hrs. Cell viability were measured using presto blue assay. RESULTS: Eleven new CAPE derivatives were synthesized. CAPE derivatives CA001, CA003, CA005, CA006, CA007, CA008, CA009, CA0013, and CA0014 reduce the viability of MM RPMI 8226 cells dose- and time-dependently. CA009 is shown to be a more potent anti-myeloma compound than its parental CAPE. Interestingly, CAPE derivatives CA002 and CA004 did not affect the viability of MM RPMI 8226 cells within the doses and incubation time examined. CONCLUSIONS: A number of CAPE derivatives synthesized exhibit cytotoxic effects in human MM cells and these results may shed a light on the structure activity relationship of CAPE.
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