Biological Activities of Chemical Constituents from the Roots of Clausena excavata Burm. f. and Their Semi-Synthetic Analogs

Abstract

Phytochemical investigation of a crude methanol extract of roots of Clausena excavata resulted in the isolation of dentatin (32), clausarin (33), nordentatin (34), xanthyletin (35), clausine K (43), heptaphylline (46), 7-methoxymukonal (77), kinocoumarin (80), and citrusarin A (115), Semi-synthetic analogs of 80, 33 and 34, compounds 80a, 33a-33d, and 34b-34d, were obtained for biological assays. Compounds 32-34, 80, 33a and 80a showed antimalarial activity against with EC50 values of >7.66, 0.58, 5.62, 1.10, 1.97 and 3.25 µM, respectively. The isolated compounds 46 and 80, and the synthetic analogs 33b, 33c, 34b and 34c, displayed stronger α-glucosidase inhibitory activity (IC₅₀ = 32.89-92.55 µM) than acarbose (IC₅₀ 391.47 μM). For nitric oxide (NO) inhibition in macrophage cells, 33 displayed the strongest activity (IC₅₀ = 27.95 µM), followed by 33d with IC50 = 33.62 µM and 34 with IC50 = 35.41 µM. These activities were 7.9-6.2 folds stronger than the positive control, diclofenac (IC₅₀ = 222.42 µM). The synthetic compounds 33b and 34b were further evaluated for their cytotoxicity against A549 cells due to their observed toxicity toward RAW 264.7 cells in the NO inhibitory activity assay. The results revealed that these two compounds were cytotoxic against A549 cells, with 33b being more effective (IC₅₀ = 11.71 µM) than cisplatin (IC50 = 21.56 µM), while the activity of 34b (IC₅₀ = 22.39 µM) was comparable to that of cisplatin.

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