Development of inhibitors against lipase and α-glucosidase from derivatives of monascus pigment

New derivatives of monascus pigment were produced during Monascus fermentation by the addition of unnatural amino acids, and the inhibitory activities of the derivatives against diet-related lipase and α-glucosidase were tested. Derivatives with penicillamine (h-Pen), cyclohexylalanine (h-Cha), butylglycine (l-t-Bg), and norleucine (h-Nle) showed relatively high inhibitory activities against lipase. The h-Pen derivative exhibited the highest inhibitory activity, with an IC₅₀ (50% inhibition) value of 24.0 μM. The four derivatives all showed noncompetitive inhibition patterns against lipase. The inhibition constant (K_i) of the h-Pen derivative was estimated to be 20.7 μM. The h-Pen derivative also exhibited a relatively high inhibitory activity against α-glucosidase, with an IC₅₀ value of 50.9 μM. The inhibition pattern of the h-Pen derivative against α-glucosidase appeared to be of a mixed type. The inhibition constants K_i and were estimated to be 25.9, and 98.9 μM, respectively.