Synthesis and biological evaluation of semi-synthetic albocycline analogs
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Authors: Daher, Samer S.; Franklin, Kevin P.; Scherzi, Tyler; Dunman, Paul M.; Andrade, Rodrigo B.
Abstract
Albocycline (ALB) is a unique macrolactone natural product with potent, narrow-spectrum activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate (VISA), and vancomycin-resistant S. aureus (VRSA) strains (MIC = 0.5-1.0 mu g/mL). Described herein is the synthesis and evaluation of a novel series analogs derived from albocycline by functionalization at three specific sites: the C2-C3 enone, the tertiary carbinol at C4, and the allylic C16 methyl group. Exploration of the structure-activity relationships (SAR) by means of minimum inhibitory concentration assays (MICs) revealed that C4 ester analog 6 was twice as potent as ALB, which represents a class of lead compound that can be further studied to address multi-drug resistant pathogens.
Seasonal variation in bioactive properties and phenolic composition of cardoon (Cynara cardunculus var. altilis) bracts
FOOD CHEMISTRY
Authors: Mandim, Filipa; Petropoulos, Spyridon A.; Dias, Maria Ines; Pinela, Jose; Kostic, Marina; Sokovic, Marina; Santos-Buelga, Celestino; Ferreira, Isabel C. F. R.; Barros, Lillian
Abstract
Cardoon (Cynara cardunculus L.) bracts were collected at different maturation stages to investigate seasonal changes in the phenolic compounds profile and in vitro bioactivities. Among the 12 phenolic compounds tentatively identified, 3,5-O-dicaffeoylquinic acid (21.83 mg/g extract) and apigenin 7-O-glucuronide (10.6 mg/g extract) were the most abundant. Immature bracts (Cl: principal growth stage (PGS) 5) had the highest phenolic compounds content, and anti-inflammatory (IC50 = 72 mu g/mL) and cytotoxic (IC50 of 30-79 mu g/mL) activities. Moreover, extract Cl inhibited efficiently the formation of thiobarbituric acid reactive substances (TBARS; IC50 = 26.8 mu g/mL), while extract C8 (PGS 8/9) was more effective against oxidative haemolysis (IC(50 )38 and 75 mu g/mL). The highest antibacterial and antifungal activities were attributed to samples C1 and C6 (PGS 7/8) and samples C2 (PGS 5/6) and C4 (PGS 6/7), respectively. Overall, the obtained results suggest the seasonal changes of polyphenolic composition and bioactivity of cardoon bracts of variable maturity.