ABSTRACT
The first total synthesis of marine natural product, (-)-majusculoic acid (1) and its seven analogs (9-15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner-Wadsworth-Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9-15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (-)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Fatty Acids, Unsaturated/chemical synthesis , Hydrocarbons, Brominated/chemical synthesis , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cell Proliferation/drug effects , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Hydrocarbons, Brominated/chemistry , Hydrocarbons, Brominated/pharmacology , Lipopolysaccharides/toxicity , Macrophages/cytology , Macrophages/drug effects , Mice , Nitric Oxide/metabolism , RAW 264.7 Cells , Structure-Activity RelationshipABSTRACT
One new (d-arabinitol-anofinicate, 1) and fourteen known (2-15) compounds were isolated from the marine Penicillium sp. MCCC 3A00228. The structure of the new compound was established mainly by extensive spectroscopic analyses. Compound 1 exhibited weak transcriptional effect on Nur77. While compound 13 showed moderate inâ vitro anti-proliferative effect against QGY7701, H1299, and HCT116 tumor cells with IC50 values of 21.2â µM, 18.2â µM, and 17.6â µM, respectively.
Subject(s)
Antineoplastic Agents/pharmacology , Penicillium/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
A unique polyketide cladosporactone A along with eight known compounds were isolated from the deep-sea-derived Cladosporium cladosporioides. The structure of cladosporactone A was established by spectroscopic analyses, and the absolute configuration was clarified by the theoretical ECD calculation. Cladosporactone A is the first member of polyketide with the 7-methylisochromen-3-one skeleton.
Subject(s)
Cladosporium/chemistry , Polyketides/chemistry , Seawater/microbiology , Circular Dichroism , Cladosporium/isolation & purification , Cladosporium/metabolism , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Polyketides/isolation & purificationABSTRACT
Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.