title: Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α.
abstract: 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 IC(50) 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.
authors.affiliation: HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. raza_shahm@yahoo.com
authors.forename: Muhammad Raza
authors.initials: MR
authors.lastname: Shah
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arfan
authors.forename: Hazrat
authors.initials: H
authors.lastname: Amin
authors.forename: Zahid
authors.initials: Z
authors.lastname: Hussain
authors.forename: Muhammad Irfan
authors.initials: MI
authors.lastname: Qadir
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
authors.forename: Donald
authors.initials: D
authors.lastname: VanDerveer
authors.forename: M Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.forename: Samreen
authors.initials: S
authors.lastname: Soomro
authors.forename: Almas
authors.initials: A
authors.lastname: Jabeen
authors.forename: Inam Ullah
authors.initials: IU
authors.lastname: Khan
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011485:Protein Binding / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
chemical_list: D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C006741:bergenin