Effects of some natural leads on Trypanosoma and Leishmania strains

Well-known medical herbal compounds including apigenin, daidzein, phyllanthin and tyramine were assessed against Trypanosoma and Leishmania protozoans. Two strains of the bloodstream forms of Trypanosoma brucei: s427-WT and TbAT1-B48, and Leishmania major and Leishmania mexicana promastigotes were utilised. Among selected natural compounds, apigenin and daidzein displayed moderate activity against African trypanosomes with EC50 16 µM for wild-type sensitive control strain. Tyramine was not found to be very active for trypanosomes strains while all compounds were found to have trivial activity for the inhibition of Leishmania mexicana strains

Effects of some natural leads on Trypanosoma and Leishmania strains

Well-known medical herbal compounds including apigenin, daidzein, phyllanthin and tyramine were assessed against Trypanosoma and Leishmania protozoans. Two strains of the bloodstream forms of Trypanosoma brucei: s427-WT and TbAT1-B48, and Leishmania major and Leishmania mexicana promastigotes were utilised. Among selected natural compounds, apigenin and daidzein displayed moderate activity against African trypanosomes with EC50 16 µM for wild-type sensitive control strain. Tyramine was not found to be very active for trypanosomes strains while all compounds were found to have trivial activity for the inhibition of Leishmania mexicana strains

Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors

Abstract: A new series of compounds based on benzodiazepine-1,2,3-triazole were synthesized and evaluated as cholinesterase inhibitors by Ellman�s method. The compounds proved to be selective inhibitors of butyrylcholinesterase (BuChE) over acetylcholinesterase. The most potent compound was 3,3-dimethyl-11-(3-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzob,e1,4diazepin-1-one, identified as a submicromolar inhibitor of BuChE with IC50 value of 0.2 µM. In addition, the amyloid-β self-aggregation evaluation studies for selected compounds showed potent inhibitory effects compared to donepezil. The docking and cell viability studies supported the potential of compound 9b-6 as significant BuChE inhibitor. Graphic abstract: Figure not available: see fulltext. © 2019, Springer Nature Switzerland AG

Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease

A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8�0.71 µM) and showed remarkable BuChE inhibition activity (IC50 = 1.9�0.006 µM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 µM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 µM) and BuChE (IC50 = 0.006 µM), respectively. The ligand�protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced.neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD. © 2021 Elsevier Inc

Thieno2,3-bpyridine amines: Synthesis and evaluation of tacrine analogs against biological activities related to Alzheimer's disease

In search of safer tacrine analogs, various thieno2,3-bpyridine amine derivatives were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs). Among the synthesized compounds, compounds 5e and 5d showed the highest activity towards acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.55 and 0.23 µM, respectively. The most active ChE inhibitors (5e and 5d) were also candidates for further complementary assays, such as kinetic and molecular docking studies as well as studies on inhibitory activity towards amyloid-beta (βA) aggregation and β-secretase 1, neuroprotectivity, and cytotoxicity against HepG2 cells. Our results indicated efficient anti-Alzheimer's activity of the synthesized compounds. © 2020 Deutsche Pharmazeutische Gesellschaf