Chemical Composition and Biological Activities of Metania and Drulia (Metaniidae) Freshwater Sponges from Amazonia.

Sponges from freshwater environments, unlike marine's, are poorly known producers of natural compounds with medicinal purposes. Amazonian sponges produce massive large specimens and are widely spread, taxonomically diverse and their metabolites could represent a new frontier on unusual natural products to treat diseases such as Alzheimer's and Malaria. Species of Metania and Drulia (Metaniidae) genera are major contributors to the fauna of Amazonian freshwater sponges. Methanolic extracts from several species from these genera had their inhibitory activities evaluated in vitro, for parasite Plasmodium falciparum and acetyl and butyrylcholinesterase enzymes (AChE and BChE). All extracts were able to inhibit AChE, although no activity was observed towards BChE. Drulia uruguayensis extract was the most potent, inhibiting AChE with IC50 =1.04 mg/mL. For antiplasmodial activity, all species showed inhibition to P. falciparum, but Metania reticulata being the most efficient with IC50 =2.7 µg/mL. Mass spectrometry analyses evidenced the presence of fatty acids and sterols in active extracts.

Evaluation of larvicidal, adulticidal, and anticholinesterase activities of essential oils of Illicium verum Hook. f., Pimenta dioica (L.) Merr., and Myristica fragrans Houtt. against Zika virus vectors.

Aedes aegypti is the vector responsible for transmitting pathogens that cause various infectious diseases, such as dengue, Zika, yellow fever, and chikungunya, worrying health authorities in the tropics. Due to resistance of mosquitoes to synthetic insecticides, the search for more effective insecticidal agents becomes crucial. The aim of this study was to verify the larvicidal, adulticidal, and anticholinesterase activities of the essential oils of the Illicium verum (EOIV), Pimenta dioica (EOPD), and Myristica fragrans (EOMF) against Ae. aegypti. The essential oils (EOs) were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The larvicidal and adulticidal activities of EOs were evaluated against third instar larvae and Ae. aegypti adult females, respectively, using the procedures of the World Health Organization (WHO) and the anticholinesterase activity of the EOs by the modified Ellman method. The following major components were identified: (E)-anethole (90.1%) for EOIV, methyl eugenol (55.0%) for EOPD, and sabinene (52.1%) for EOMF. All EOs exhibited larvicidal and adulticidal activity against Ae. aegypti. The highest larval mortality was observed in EOMF with LC50 = 28.2 µg mL-1. Adult mortality was observed after 1 (knockdown) and 24 h exposure, with the highest potential established by the EOIV, KC50 = 7.3 µg mg female-1 and LC50 = 10.3 µg mg female-1. EOIV (IC50 = 4800 µg mL-1), EOMF (IC50 = 4510 µg mL-1), and EOPD (IC50 = 1320 µg mL-1) inhibited AChE. EOMF (4130 µg mL-1) and EOPD (IC50 = 3340 µg mL-1) inhibited BChE whereas EOIV showed no inhibition. The EOs were toxic to larvae and adults of Ae. aegypti, as well as being less toxic to humans than the currently used insecticides, opening the possibility of elaboration of a natural, safe, and ecological bioinsecticide for vector control.

New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer's disease: Synthesis, molecular modeling, NMR, and biological evaluation.

Two new compounds (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2H)-ylidene)hydrazinecarbothiomide (3) and (E)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2H)-ylidene)hydrazinecarboxamide (4) were synthesized and evaluated for their anticholinesterase activities. In vitro tests performed by NMR and Ellman's tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE. Also, in silico toxicity evaluation suggested that these new compounds can be less toxic than tacrine.