ABSTRACT
We synthesized seven (Z)-benzylidene-2-(E)-styryloxazol-5(4H)-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 µM, showed an affinity (Ki) from 2 to 198 µM, and an IC50 from 9 to 246 µM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds. In addition, in silico pharmacokinetic analysis was carried out to predict the compounds' blood-brain barrier (BBB) permeability. The most potent inhibitor of hAChE significantly improved cognitive impairment in a modified Y-maze test (5 µmol/kg) and an Object Recognition Test (10 µmol/kg). Our results can help the rational design of hAChE inhibitors to work as potential candidates for treating cognitive disorders.
Subject(s)
Acetylcholinesterase , Alzheimer Disease , Animals , Mice , Humans , Acetylcholinesterase/metabolism , Molecular Docking Simulation , Oxazolone , Cholinesterase Inhibitors/chemistry , Disease Models, Animal , Cognition , Structure-Activity RelationshipABSTRACT
In the current study, chemical composition of cultivated Salvia canariensis L was determined. Carnosol was the main product isolated. We prepared more lipophilic derivatives from carnosol, and both isolated and semisynthetic abietane diterpenes were evaluated in vitro as inhibitors of squalene synthase. Among the compounds tested, carnosol was the most potent inhibitor (IC50 = 17.6 µM). These results highlight the great potential of this species for the production of new ingredients in nutritional supplements for the treatment of hyperlipidemia.
Subject(s)
Abietanes/pharmacology , Diterpenes , Farnesyl-Diphosphate Farnesyltransferase/antagonists & inhibitors , Salvia , Abietanes/isolation & purification , Animals , Diterpenes/isolation & purification , Diterpenes/pharmacology , Liver/enzymology , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Rats , Salvia/chemistryABSTRACT
The available scientific literature regarding tanshinones is very abundant, and after its review, it is noticeable that most of the articles focus on the properties of tanshinone I, cryptotanshinone, tanshinone IIA, sodium tanshinone IIA sulfonate and the dried root extract of Salvia miltiorrhiza (Tan- Shen). However, although these products have demonstrated important biological properties in both in vitro and in vivo models, their poor solubility and bioavailability have limited their clinical applications. For these reasons, many studies have focused on the search for new pharmaceutical formulations for tanshinones, as well as the synthesis of new derivatives that improve their biological properties. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2015) on tanshinones in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we offer an update on the last five years of new research on these quinones, focusing on their synthesis, biological activity on noncommunicable diseases and drug delivery systems, to support future research on its clinical applications.
