EXTRACTS FROM CALCEOLARIA TALCANA EXHIBITED STRONG BIOINSECTICIDAL EFFECTS AGAINST DROSOPHILA MELANOGASTER AND SPODOPTERA FRUGIPERDA. THE MOST ACTIVE EXTRACT WAS ETHYL ACETATE AND ITS MAJORITY COMPOUND VERBASCOSIDE. THE HIGHEST LETHAL CONCENTRATION TO THE LARVAE OF S. FRUGIPERDA AND D. MELANOGASTER WAS 20.0 ?G/ML OF THE ETHYL ACETATE EXTRACT WITH 95.8% AND 67.0% OF MORTALITY, RESPECTIVELY. AGAINST D. MELANOGASTER THE ETHYL ACETATE EXTRACT SHOWED THE HIGHEST ACTIVITY WITH 75.05% OF ANTIFEEDANT INDEX AT 25 ?G/ML, METHANOL EXTRACT INSTEAD SHOWED 100% TO 100 ?G/ML. AT VERY LOW CONCENTRATIONS ETHYL ACETATE AND METHANOL EXTRACTS INDUCE ANTIFEEDANT AND INSECT GROWTH REGULATORY ACTIVITY SHOWING SELECTIVE EFFECTS AS DETERRENT AND ON THE SCLEROTIZATION SHOWING A PRE-EMERGENCE EFFECT ON S. FRUGIPERDA. THE RESULTS FROM THESE EXTRACTS WERE BETTER THAN SHOWED BY METHANOL EXTRACTS FROM CEDRELA SALVADORENSIS, MYRTILLOCACTUS GEOMETRIZANS AND YUCCA PERICULOSA SAMPLES USED AS POSITIVE CONTROLS.

THE CHILEAN PLANTS DISCARIA CHACAYE, TALGUENEA QUINQUENERVIA (RHAMNACEAE), PEUMUS BOLDUS (MONIMIACEAE), AND CRYPTOCARYA ALBA (LAURACEAE) WERE EVALUATED AGAINST CODLING MOTH: CYDIA POMONELLA L. (LEPIDOPTERA: TORTRICIDAE) AND FRUIT FLY DROSOPHILA MELANOGASTER (DIPTERA: DROSOPHILIDAE), WHICH IS ONE OF THE MOST WIDESPREAD AND DESTRUCTIVE PRIMARY PESTS OF PRUNUS (PLUMS, CHERRIES, PEACHES, NECTARINES, APRICOTS, ALMONDS), PEAR, WALNUTS, AND CHESTNUTS, AMONG OTHER. FOUR BENZYLISOQUINOLINE ALKALOIDS (COCLAURINE, LAUROLITSINE, BOLDINE, AND PUKATEINE) WERE ISOLATED FROM THE ABOVE MENTIONED PLANT SPECIES AND EVALUATED REGARDING THEIR INSECTICIDAL ACTIVITY AGAINST THE CODLING MOTH AND FRUIT FLY. THE RESULTS SHOWED THAT THESE ALKALOIDS POSSESS ACUTE AND CHRONIC INSECTICIDAL EFFECTS. THE MOST RELEVANT EFFECT WAS OBSERVED AT 10 ?G/ML AGAINST D. MELANOGASTER AND AT 50 ?G/ML AGAINST C. POMONELLA, BEING THE ALTERATION OF THE FEEDING, DEFORMATIONS, FAILURE IN THE DISPLACEMENT OF THE LARVAE IN THE FEEDING MEDIUM OF D. MELANOGASTER, AND MORTALITY VISIBLE EFFECTS. IN ADDITION, THE DOCKING RESULTS SHOW THAT THESE TYPE OF ALKALOIDS PRESENT A GOOD INTERACTION WITH OCTOPAMINE AND ECDYSONE RECEPTOR SHOWING A POSSIBLE ACTION MECHANISM.

THE PURPOSE OF THIS STUDY WAS TO DETERMINE THE INHIBITORY CAPACITY OF CEANOTHANES TRITERPENES ISOLATE FROM CHILEAN RHAMNACEAE ON ACETYLCHOLINESTERASE (ACHE) AND BUTYRYLCHOLINESTERASE (BCHE) ENZYMES. SEVEN CEANOTHANES TRITERPENES WERE ISOLATED FROM AERIAL PARTS OF PLANT MATERIAL BY CLASSICAL PHYTOCHEMICAL METHODS OR PREPARED BY THE HEMISYNTHETIC METHOD. STRUCTURES WERE DETERMINED BY THE SPECTROSCOPIC METHOD (1H-NMR AND 13C NMR) AND MASS SPECTROMETRY (MS). ACHE AND BCHE ACTIVITY WERE DETERMINED BY THE ELLMANN METHOD FOR ALL COMPOUNDS. ALL TESTED COMPOUNDS EXERTED A GREATER AFFINITY TO ACHE THAN TO BCHE, WHERE COMPOUND 3 HAS AN IC50 OF 0.126 UM FOR ACHE AND OF >500 UM TO BCHE. KINETIC STUDIES INDICATED THAT ITS INHIBITION WAS COMPETITIVE AND REVERSIBLE. ACCORDING TO THE MOLECULAR COUPLING AND DISPLACEMENT STUDIES OF THE PROPIDIUM IODIDE TEST, THE INHIBITORY EFFECT OF COMPOUND 3 WOULD BE PRODUCED BY INTERACTION WITH THE PERIPHERAL ANIONIC SITE (PAS) OF ACHE. THE COMPOUNDS TESTED (1?7) SHOWED AN IMPORTANT INHIBITORY ACTIVITY OF ACHE, BINDING TO PAS. THEREFORE, INHIBITORS THAT BIND TO PAS WOULD PREVENT THE FORMATION OF THE ACHE-A? COMPLEX, CONSTITUTING A NEW ALTERNATIVE IN THE TREATMENT OF ALZHEIMER?S DISEASE (AD).

CARBOHYDRATES FROM LIGNOCELLULOSIC FEED CAN BE RELEASED BY BASIDIOMYCETE FUNGI FOR RUMINAL FERMENTATION. THIS STUDY AIMED TO EVALUATE THE BIOCONVERSION OF HAY OF RYEGRASS-FESCUE (LOLIUM PERENNE?FESTUCA ARUNDINÁCEA) BY SOLID STATE FERMENTATION WITH PLEUROTUS OSTREATUS, TO OBTAIN SUPERIOR QUALITY HAY. AFTER ONLY 14 DAYS OF FERMENTATION, CRUDE PROTEIN (CP) (4.73 TO 5.16%), AND NON-FIBROUS CARBOHYDRATES (NFC) (20.84 TO 25.04%) INCREASED, WHILE NEUTRAL DETERGENT FIBER (NDF) (68.72 TO 64.87%) AND ACID DETERGENT LIGNIN (5.88 TO 1.98%) DECREASED. THE ENZYMATIC BIODEGRADATION CARRIED OUT BY P. OSTREATUS WAS VERIFIED, THROUGH MEASUREMENTS OF ENZYMATIC ACTIVITY. LIGNIN PEROXIDASE (LIP) AND LACCASE (LAC) REACHED THE HIGHER ACTIVITY ON DAY 14 (19.51 U/L AND 34.17 U/L, RESPECTIVELY), WHEREAS MANGANESE PEROXIDASE (MNP) DISPLAYED STABILITY UP TO 21 DAYS OF FERMENTATION (BETWEEN 6.54 AND 7.75 U/L). IN CONCLUSION, RESULTS INDICATE THAT LIGNOCELLULOSIC FEED BIOCONVERSION BY P. OSTREATUS IS PROMISING TO IMPROVE THE RUMINAL FERMENTATION OF FIBROUS FEEDSTOCKS AND 14 DAYS WERE CONSIDERED TO BE OPTIMAL FOR HAY FERMENTATION.

ALZHEIMER?S DISEASE (AD) IS A MULTIFACTORIAL AND FATAL NEURODEGENERATIVE DISORDER. ACETYLCHOLINESTERASE (ACHE) PLAYS A KEY ROLE IN THE REGULATION OF THE CHOLINERGIC SYSTEM AND PARTICULARLY IN THE FORMATION OF AMYLOID PLAQUES; THEREFORE, THE INHIBITION OF ACHE HAS BECOME ONE OF THE MOST PROMISING STRATEGIES FOR THE TREATMENT OF AD, PARTICULARLY CONCERNING ACHE INHIBITORS THAT INTERACT WITH THE PERIPHERAL ANIONIC SITE (PAS). CEANOTHIC ACID ISOLATED FROM THE CHILEAN RHAMNACEAE PLANTS IS AN INHIBITOR OF ACHE THROUGH ITS INTERACTION WITH PAS. IN THIS STUDY, SIX CEANOTHIC ACID DERIVATIVES WERE PREPARED, AND ALL SHOWED INHIBITORY ACTIVITY AGAINST ACHE. THE STRUCTURAL MODIFICATIONS WERE PERFORMED STARTING FROM CEANOTHIC ACID BY APPLICATION OF SIMPLE SYNTHETIC ROUTES: ESTERIFICATION, REDUCTION, AND OXIDATION. ACHE ACTIVITY WAS DETERMINED BY THE ELLMANN METHOD FOR ALL COMPOUNDS. KINETIC STUDIES INDICATED THAT ITS INHIBITION WAS COMPETITIVE AND REVERSIBLE. ACCORDING TO THE MOLECULAR COUPLING AND DISPLACEMENT STUDIES OF THE PROPIDIUM IODIDE TEST, THE INHIBITORY EFFECT OF COMPOUNDS WOULD BE PRODUCED BY INTERACTION WITH THE PAS OF ACHE. IN SILICO PREDICTIONS OF PHYSICOCHEMICAL PROPERTIES, PHARMACOKINETICS, DRUG-LIKENESS, AND MEDICINAL CHEMISTRY FRIENDLINESS OF THE CEANOTHANE DERIVATIVES WERE PERFORMED USING THE SWISS ADME TOOL.

CYCLOPEPTIDE ALKALOIDS WITH DIFFERENT BIOLOGICAL ACTIVITIES ARE PRESENT IN PLANTS OF THE FAMILY RHAMNACEAE. PLANTS OF THIS FAMILY GROW IN A SYMBIOTIC RELATIONSHIP WITH AEROBIC GRAM-POSITIVE ACTINOMYCETES BELONGING TO THE GENUS FRANKIA. THIS GOAL OF THIS RESEARCH WAS A STUDY OF THE COMPARATIVE PROFILE OF ALKALOIDS PRESENT IN DISCARIA CHACAYE AND TO ESTABLISH A CONNECTION BETWEEN THE PRESENCE OR ABSENCE OF FRANKIA SP. AND THE ALKALOIDS. IN ADDITION, INSECTICIDAL ACTIVITIES OF THE ALKALOIDAL EXTRACT WERE EXAMINED. A TOTAL OF 24 ALKALOIDS WERE IDENTIFIED, OF WHICH 12 HAVE A BENZYLISOQUINOLINE SKELETON, 9 WERE CYCLOPEPTIDES, 2 ISOQUINOLINES, AND 1 APORPHINE. THE PRESENCE OF CYCLOPEPTIDE ALKALOIDS IS ASSOCIATED WITH FRANKIA NODULES IN THE PLANT ROOT. THE ALKALOID EXTRACTS SHOWED INSECTICIDAL ACTIVITY WITH MORTALITY DOSE-DEPENDENCE AND LD50 VALUES BETWEEN 44 TO 71 ?G/ML.

NATURAL CHOLINESTERASE INHIBITORS HAVE BEEN FOUND IN MANY BIOLOGICAL SOURCES. NINE COMPOUNDS WITH AGAROFURAN (EPOXYEUDESMANE) SKELETONS WERE ISOLATED FROM SEEDS AND AERIAL PARTS OF MAYTENUS DISTICHA AND EUONYMUS JAPONICUS. THE IDENTIFICATION AND STRUCTURAL ELUCIDATION OF COMPOUNDS WERE BASED ON SPECTROSCOPIC DATA ANALYSES. ALL COMPOUNDS HAD INHIBITORY ACETYLCHOLINESTERASE (ACHE) ACTIVITY. THESE NATURAL COMPOUNDS, WHICH POSSESSED MIXED OR UNCOMPETITIVE MECHANISMS OF INHIBITORY ACTIVITY AGAINST ACHE, MAY BE CONSIDERED AS MODELS FOR THE DESIGN AND DEVELOPMENT OF NEW NATURALLY OCCURRING DRUGS FOR MANAGEMENT STRATEGIES FOR NEURODEGENERATIVE DISEASES. THIS IS THE FIRST REPORT OF THESE CHEMICAL STRUCTURES FOR SEEDS OF M. DISTICHA.

IN ORDER TO FIND MOLECULES OF NATURAL ORIGIN WITH POTENTIAL BIOLOGICAL ACTIVITIES, WE ISOLATE AND SYNTHESISE COMPOUNDS WITH AGAROFURAN SKELETONS (EPOXYEUDESMANES). FROM THE SEEDS OF MAYTENUS DISTICHA AND MAYTENUS MAGELLANICA WE OBTAINED SIX DIHYDRO-?-AGAROFURANS, AND BY MEANS OF THE ROBINSON ANNULATION REACTION WE SYNTHESISED FIVE COMPOUNDS WITH THE SAME SKELETON. THE STRUCTURES WERE ESTABLISHED ON THE BASIS OF NMR, IR, AND MS. THE EVALUATED COMPOUNDS SHOWED INHIBITORY ACTIVITY ON THE ACETYLCHOLINESTERASE ENZYME AND ON THE COX ENZYMES. COMPOUND 4 EMERGED AS THE MOST POTENT IN THE ACETYLCHOLINESTERASE INHIBITION ASSAY WITH IC50 17.0 ± 0.016 ?M ON ACETYLCHOLINESTERASE (ACHE). THE COMPOUNDS EVALUATED WERE SHOWN TO BE SELECTIVE FOR ACHE. THE MOLECULAR DOCKING, AND THE PROPIDIUM DISPLACEMENT ASSAY SUGGESTED THAT THE COMPOUNDS DO NOT BIND TO THE ACTIVE SITE OF THE ENZYME ACHE, BUT RATHER BIND TO THE PERIPHERAL ANIONIC SITE (PAS) OF THE ENZYME, ON THE OTHER HAND, THE NATURAL COMPOUND 8, SHOWED THE BEST INHIBITORY ACTIVITY ON THE COX-2 ENZYME WITH AN IC50 VALUE OF 0.04 ± 0.007 ?M. THE PHARMACOKINETIC PROFILE CALCULATED IN SILICO USING THE SWISSADME PLATFORM SHOWS THAT THESE MOLECULES COULD BE CONSIDERED AS POTENTIAL DRUGS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES SUCH AS AD.

AS A DEFENSE MECHANISM OF THE AERIAL PARTS OF CALCEOLARIA TALCANA (CALCEOLARIACEAE; FORMERLY SCROPHULARIACEAE) AGAINST HERBIVORE OFFENSES AND INSECT PEST ATTACK, DITERPENOIDS, TRITERPENOIDS, PHENYLETHANOIDS, FLAVONOIDS, AND IRIDOIDS ARE RAPIDLY ACCUMULATED ALONG THE AERIAL PARTS, RESULTING IN A UNIQUE NATURAL BIOPESTICIDE COMPLEX FROM THIS PLANT. IN ADDITION TO VERBASCOSIDE A SERIES OF KNOWN COMPOUNDS WERE SCREENED FOR THEIR INHIBITORY ACTIVITY AGAINST MUSHROOM TYROSINASE AND PROTEASE ENZYMES. ETHYL ACETATE AND N-HEXANE EXTRACTS, TOGETHER WITH CYCLOPROPYL-7,15-ENT-PIMARADIENE (1), ABIETATRIENE (2), URSOLIC ACID (3), ?-LUPEOL (4), ?-SITOSTEROL (5), 2-HYDROXY-3-(1,1-DIMETHYLALLYL)-1,4-NAPHTHOQUINONE (6), ?-DUNNIONE (7), VERBASCOSIDE (8), MARTYNOSIDE (9), AND SOME KNOWN MODEL COMPOUNDS PROVED TO BE INHIBITORS OF OXIDATION OF L-3,4-DIHYDROXYPHENYLALANINE (L-DOPA) CATALYZED BY TYROSINASE (EC 1.14.18.1) WITH AN IC50 BETWEEN 10.0 AND 200 PPM OR ?M, RESPECTIVELY, SUGGESTING THAT PHENOLIC MOIETIES IN THE MOLECULES ASSAYED ARE IMPORTANT FOR THE ACTIVITY.