Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α

Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1–15 in the respiratory burst assay. Bergenin was isolated from the crude extract of Mallotus philippenensis after repeated column chromatography and was then subjected to chemical derivatization. The structures of all compounds were elucidated by NMR and mass spectroscopic techniques. Compound 2 was also studied using single crystal X-ray diffraction. Compounds 4, (54.5 ± 2.2%) 5 (47.5 ± 0.5%) 5, and 15 (86.8 ± 1.9%) showed significant (P ⩽ 0.005) NO inhibitory activities whereas 6, 7, 11, 12 and 13 displayed moderate inhibitory activities that ranges between 16% and 31%. Furthermore compounds 4 and 15, were discovered as significant (P ⩽ 0.005) TNF-α inhibitors with 98% and 96% inhibition, respectively, while compounds 3, 5, 7, 8, 11, and 12 showed low level of TNF-α inhibition (0.4–28%). Compounds 8, 13 and 15 exhibited moderate anti-inflammatory IC50 activities with 212, 222, and 253 μM, respectively, compared to the standard anti-inflammatory drug indomethacin as well as the parent bergenin compound. No cytotoxic effects could be detected when the compounds were tested on 3T3 cells up to concentrations of 100 μM.

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