Antioxidant and antiradical activities of flavonoids.

The relationship between the structure of 42 flavonoids and their antioxidant and antiradical activities was elucidated by heat-induced oxidation in a beta-carotene and linoleic acid system and by the 1,1-diphenyl-2-picrylhydrazyl decoloration test. From seven structurally divergent groups of flavonoids, only flavonols with a free hydroxyl group at the C-3 position of the flavonoid skeleton showed high inhibitory activity to beta-carotene oxidation. Antiradical activity depended on the presence of a flavonol structure or free hydroxyl group at the C-4' position. The effect of the 4'-hydroxyl was strongly modified by other structural features, such as the presence of free hydroxyls at C-3 and/or C-3' and a C2-C3 double bond.     

Chemical restraint of African mole‐rats (Fukomys sp.) with a combination of ketamine and xylazine

ObjectiveTo establish an accurate anaesthetic dose for chemical restraint of African mole-rats using ketamine and xylazine.Study designProspective nonrandomized laboratory study.AnimalsSixteen adult Ansell’s mole-rats (Fukomys anselli) and eight giant mole-rats (F. mechowii).MethodsFukomys anselli of different ages, sexes and reproductive status were systematically anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg⁻¹) and increasing the doses in steps of 0.5 mg kg⁻¹ until loss of the righting reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine, starting at 0.5 mg kg⁻¹ that was increased by 0.5 mg kg⁻¹ in further trials. Once an effective combination was established and evaluated in F. anselli, it was also tested in F. mechowii. Heart and respiratory rates and rectal temperatures were measured during anaesthesia. anova for repeated measures and Student’s t-test were used to compare means.ResultsChemical restraint was accomplished at a dose of 6 mg kg⁻¹ ketamine combined with 2.5 mg kg⁻¹ xylazine. LRR lasted on average mean 56 ± SD 19 minutes (F. anselli) and 140 ± 41 minutes (F. mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 ± 15 minutes (F. anselli) and for 29 ± 2 minutes (F. mechowii), respectively. All animals recovered satisfactorily. Heart and respiratory rates were stable during anaesthesia, but rectal temperature fell significantly in F. mechowii after losing the righting reflex (LRR) from T1 (32.6 ± 0.6 °C) to T3 (30.4 ± 0.9 °C).Conclusions and Clinical relevanceAfrican mole-rats (Bathyergidae) live in closed burrow systems under particular conditions (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several physiological adaptations. Injectable anaesthetics in the dose rates used in other rodents are not appropriate for use in these subterranean species. Here, a reliable protocol for chemical restraint is provided.     

Epigenetic tailoring for the production of anti-infective cytosporones from the marine fungus Leucostoma persoonii

Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B (1, 360%), C (2, 580%) and E (3, 890%), as well as the production of the previously undescribed cytosporone R (4). Cytosporone E was the most bioactive, displaying an IC(90) of 13 μM toward Plasmodium falciparum, with A549 cytotoxicity IC(90) of 437 μM, representing a 90% inhibition therapeutic index (TI(90) = IC(90) A459/IC(90)P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 μM and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 μM).