6820-93-5Relevant articles and documents
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates
Piemontese, Luca,Tomás, Daniel,Hiremathad, Asha,Capriati, Vito,Candeias, Emanuel,Cardoso, Sandra M.,Chaves, Sílvia,Santos, M. Amélia
, p. 1212 - 1224 (2018)
A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0–30.0?μΜ) and moderate ability for inhibition of Aβ1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.
Synthesis, characterization and X-ray crystal structure of potentially N6O2 coordinating macroacyclic Schiff base ligands and their Mn(II), Zn(II) and Cd(II) complexes; cytotoxic, antibacterial properties and competitive 7Li NMR studies
Forouzandeh, Fatemeh,Keypour, Hassan,Zebarjadian, Mohammad Hasan,Mahmoudabadi, Masoumeh,Hosseinzadeh, Leila,Karamian, Roya,Ahmadi Khoei, Masoumeh,Gable, Robert William
, p. 238 - 246 (2019)
In this work, two new symmetrical, potentially N6O2 coordinating, macroacyclic Schiff base ligands (H2L1 and H2L2) were derived from the condensation of a newly synthesized polyamine, 2,2′-(ethane-1,2-diylbis(piperazine-4,1-diyl))bis(ethan-1-amine) (A), with 2-hydroxybenzaldehyde and 2-hydroxy-3-methoxybenzaldhyde respectively. Six macroacylic Schiff base complexes were prepared by direct reaction of H2L1 or H2L2 with Mn(II), Zn(II) or Cd(II) metal ions in equimolar ratios. The products were characterized by several physicochemical measurements. As well, the crystal structure of H2L1 was confirmed by a single crystal X-ray structural analysis. Competitive 7Li NMR experiments were used to probe the complexation of Mn2+, Zn2+ and Cd2+ ions with (H2L1) and (H2L2) in both acetonitrile and methanol. The stabilities of the final complexes were found to be in the order M–(H2L1) > M–(H2L2) and Cd2+ > Zn2+ > Mn2+. The cytotoxic and antibacterial properties of these complexes were also investigated.
New approach to address antibiotic resistance: Miss loading of functional membrane microdomains (FMM) of methicillin-resistant Staphylococcus aureus (MRSA)
Nagendra Prasad,Karthik,Manukumar,Mallesha,Mallu
, p. 106 - 115 (2019)
The synthesized potent piperazine analog ChDiPiCa was characterised by various spectroscopic techniques and for the first time evaluated functional membrane microdomain (FMM) disassembly in methicillin-resistant Staphylococcus aureus (MRSA). The ChDiPiCa showed excellent in vitro biocidal activity against MRSA at 26 μg/mL compared to the antibiotic streptomycin and bacitracin 14 μg/mL and 13 μg/mL at 10 μg concentration respectively. The membrane damaging property was confirmed by the SEM analysis. Further, we addressed the new approach for the first time to overcome antibiotic resistance of MRSA through membrane microdomain miss loading to lipids. By which, the ChDiPiCa confirms the significant activity in miss loading of FMM of MRSA which is validated by the fatty acid profile and lipid analysis. The result shows that, altered saturated (Lauric acid and Myristic acid), mono unsaturated (Oleic acid), and poly unsaturated (Linoleic acid and Linolenic acid) fatty acids and hypothesises, altered the membrane functional lipids. For the better understanding of miss loading of FMM by the ChDiPiCa, the in-silico molecular docking studies was analyzed and confirmed the predicted role. This suggests the way to develop ChDiPiCa in medicinal chemistry as anti-MRSA candidates and also this report opens up new window to treat microbial pathogens and infections.
Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2‐Hydroxyphenylbenzimidazole-based Scaffolds en Route to Donepezil‐Like Compounds
Amélia Santos, M.,Brunetti, Leonardo,Capriati, Vito,Perna, Filippo M.,Piemontese, Luca,Rinaldo, Federica,Sergio, Roberta
, (2020/02/06)
An unsubstituted 2‐hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi‐target ligand in Alzheimer’s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so‐called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio‐renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2‐hydroxyphenylbenzimidazole‐based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure‐activity relationships (SARs).
