Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer’s disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood–brain barrier, qualifying as leads for new drugs against AD. Evaluation of their inhibitory capacity against acetyl- and butyrilcholinesterases (AChE and BChE) through Ellmann’s test showed that three compounds present promising results with one of them being capable of inhibiting both enzymes. Further docking studies of the six compounds synthesized helped to elucidate the main interactions that may be responsible for the inhibitory activities observed.

The development of pharmacological agents for the treatment of Alzheimer's Disease (AD) is very relevant since this is the most common type of dementia. The inhibition of acetylcholinesterase (AChE) is important to increase the low levels of acetylcholine (ACh) neurotransmitter observed in sick people, which is associated with the memory loss. In this work, a new guanylhydrazone was designed and synthesized as an AChE inhibitor. This new compound was compared to tacrine and other guanylhydrazones. All of them were studied by molecular docking and tested in vitro as AChE inhibitors by Ellman's test and Fig-NMR method. A high inhibition of AChE by the new compound was observed, showing that this compound has great potential for the treatment of AD.

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.

The compounds 7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (5) and 5-[-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione (7), were synthesized from dimedone and barbituric acid and had their three-dimensional structures and precise chemical shifts assignments obtained by Nuclear Magnetic Resonance (NMR) from ¹H, ¹³C, APT, COSY, HSQC, and HMBC spectra. Additional HOMO-LUMO DFT calculations corroborated the NMR results and pointed to the most stable stereoisomers of each compound. Besides, further docking and molecular dynamic studies suggest that the stereoisomers (9S)-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)-3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one, and 5-[(5S)-7-chloro-2,4-dioxo-1H, 2H, 3H, 4H, 5H-chromeno[2,3-d]pyrimidin-5-yl)]-1,3-diazinane-2,4,6-trione of these compounds may act as DNA intercalators and qualify as potential leads for the development of new anticancer drugs. Communicated by Ramaswamy H. Sarma

Bees are becoming more and more valued for the extremely important role they play in ecological communities, especially for their pollinating action. The state of Roraima, Brazil has areas of native vegetation and variety of stingless bees, and this potential is still untapped. The objective of this study was to determine the chemical composition of materials collected from the nests of Frieseomelitta silvestrii (FRIESE, 1902), identified in São Luiz, in Roraima state, Brazil. The chemical composition of the collected material was determined by gas chromatography coupled to mass spectrometry (GC-MS). The dichloromethane extracts of propolis, cerumen threads and resin present in the stingless bee nest presented differentiated profiles with the occurrence of low polarity compounds.