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A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3C pro ) and anti-enterovirus 71 (EV71) activity in vitro . Molecular docking revealed that 5s (IC 50 = 0.22 ± 0.07 μM, EC 50 = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3C pro , which was consistent with the biological data compared to reference 5a (IC 50 = 0.54 ± 0.02 μM, EC 50 = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC 50 = 0.10 ± 0.02 μM, EC 50 = 0.11 ± 0.07 μM), which exhibited the most potent 3C pro inhibitory and antiviral activity. [ABSTRACT FROM AUTHOR]

A series of polyamine conjugates of flavonoids with a naphthalene motif were synthesized and evaluated for their anti-hepatocellular carcinoma properties using in vitro and in vivo assays. Compound 8a displayed favorable selectivity between hepatocellular carcinoma cells and normal hepatocyte cells, and the combination of 8a with aspirin resulted in additive inhibition of in vitro tumor cell growth and migration. The 8a -aspirin combination also inhibited H22 liver tumor growth and pulmonary metastasis and improved body weight index in animal models. Preliminary mechanistic studies indicated that 8a increased the expression of apoptosis-related proteins such as p-p38, p-JNK, p53 and Bcl-2, an effect that was further amplified by aspirin. Therefore, a cocktail therapy of flavonoid-polyamine conjugates with aspirin has potential use as an antitumor therapy. [ABSTRACT FROM AUTHOR]