Toksično djelovanje ekstrakta cvijeta Prunus spinosa L. na stanice hepatokarcinoma

Prunus spinosa L. (blackthorn) is used in traditional medicine as a remedy for various diseases. To establish its anticancer properties, we exposed human liver cancer cells (Hep G2) to a range of blackthorn flower extract concentrations (10-200 μg/mL) and determined cytotoxic activity with the neutral red and kenacid blue methods after 24, 48, and 72 h of incubation. Statistically significant inhibitory effects on Hep G2 cellular proliferation were observed at concentrations above 50 μg/mL (p<0.001–0.05). Cell viability was lower when determined with neutral red than kenacid blue method. In addition, we evaluated antioxidant/ prooxidant effects of the blackthorn flower extract by measuring reactive oxygen species (ROS), and the results confirmed its prooxidant behaviour within the applied concentration range. Flow cytometry determined primarily necrotic and apoptotic cell death, which provides additional evidence of its cytotoxic effect on liver carcinoma.Prunus spinosa L. (trnina) biljka je koja se koristi u tradicionalnoj medicini kao lijek za različite bolesti. Da bi se utvrdila njezina antikancerogena svojstva, kao model korištene su stanice humanoga hepatocelularnoga karcinoma (Hep G2) koje su izložene ekstraktu cvijeta trnine u koncentracijama 10–200 μg/mL te je određena citotoksična aktivnost s kenacid blue i neutral red metodama nakon 24, 48 i 72 sata inkubacije. Statistički značajni inhibitorni učinci na staničnu proliferaciju uočeni su pri koncentracijama iznad 50 μg/mL (p<0,001–0,05). Vijabilnost stanica određena metodom neutral red bila je niža u odnosu na onu koja je određena kenacid blue metodom. Dodatno su ispitani antioksidacijski/prooksidacijski učinci ekstrakta cvijeta trnine mjerenjem reaktivnih kisikovih vrsta (ROS), a rezultati su potvrdili prooksidacijsko djelovanje u primijenjenom rasponu koncentracija. Protočnom citometrijom detektiran je visok udio stanica u apoptozi i nekrozi, što dodatno upućuje na citotoksičnost u stanicama karcinoma jetre

Intramolecular Modulation of Serine Protease Inhibitor Activity in a Marine Cyanobacterium with Antifeedant Properties

Extracts of the Floridian marine cyanobacterium Lyngbya cf. confervoides were found to deter feeding by reef fish and sea urchins (Diadema antillarum). This antifeedant activity may be a reflection of the secondary metabolite content, known to be comprised of many serine protease inhibitors. Further chemical and NMR spectroscopic investigation led us to isolate and structurally characterize a new serine protease inhibitor 1 that is formally derived from an intramolecular condensation of largamide D (2). The cyclization resulted in diminished activity, but to different extents against two serine proteases tested. This finding suggests that cyanobacteria can endogenously modulate the activity of their protease inhibitors

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2

Nonhalogenated organic molecules from Laurencia algae

The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C15-acetogenins, are described.The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C-15-acetogenins, are described