03072nas a2200313   4500008004100000022001400041245014000055210006900195260000900264300001100273490000800284520201300292653001602305653002802321653002002349653001902369653002202388653002402410100001602434700002402450700001902474700002502493700002002518700001902538700002202557700002902579700001902608856013102627       2023                        eng d  a0141-813000aDesign and synthesis of piano-stool ruthenium(II) complexes and their studies on the inhibition of amyloid ? (1-42) peptide aggregation0 aDesign and synthesis of pianostool rutheniumII complexes and the  cJUN   a1241970 v2393 a<p>
	Misfolding , protein aggregation have been linked to numerous human neurodegenerative disorders such as Alzheimer's, prion , Parkinson's diseases. Ruthenium (Ru) complexes have received considerable attention in studying protein aggregation due to their interesting photophysical and photo properties. In this study, we have synthesized the novel Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6](Ru-1), and [Ru(p-cymene)Cl(L-2)][PF6](Ru-2)) and investigated their inhibitory activity against the bovine serum albumin (BSA) aggregation and the A beta 1-42 peptides amyloid formation. Several spectroscopic methods were used to characterize these complexes, and the molecular structure of the complex was determined by X-ray crystallography. Amyloid aggregation and inhi-bition activities were examined using the Thioflavin-T (ThT) assay, and the secondary structures of the protein were analyzed by circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The cell viability assay was carried out on the neuroblastoma cell line, revealing that the complex Ru-2 showed better protective effects against A beta 1-42 peptide toxicity on neuro-2a cells than the complex Ru-1. Molecular docking studies elucidate the binding sites and interactions between the Ru-complexes and A beta 1-42 peptides. The exper-imental studies revealed that these complexes significantly inhibited the BSA aggregation and A beta 1-42 amyloid fibril formation at 1:3 and 1:1 molar concentrations, respectively. Antioxidant assays demonstrated that these complexes act as antioxidants, protecting from amyloid-induced oxidative stress. Molecular docking studies with the monomeric A beta 1-42 (PDB: 1IYT) show hydrophobic interaction, and both complexes bind preferably in the central region of the peptide and coordinate with two binding sites of the peptide. Hence, we suggest that the Ru-based complexes could be applied as a potential agent in metallopharmaceutical research against Alzheimer's disease.</p>
10aAggregation10aAmyloid ?(1-42) peptide10aDFT computation10aFibrillization10aMolecular docking10aRuthenium complexes1 aSingh, Sain1 aNavale, Govinda, R.1 aAgrawal, Sonia1 aSingh, Haobam, Kisan1 aSingla, Labhini1 aSarkar, Dhiman1 aSarma, Manabendra1 aChoudhury, Anghuman, Roy1 aGhosh, Kaushik  uhttps://library.ncl.res.in/content/design-and-synthesis-piano-stool-rutheniumii-complexes-and-their-studies-inhibition-amyloid02379nas a2200277   4500008004100000022001400041245010700055210007000162260000900232300001100241490000800252520144600260653002501706653003801731653002201769100001701791700002401808700001601832700002501848700001901873700001901892700001901911700002201930700001901952856013001971       2023                        eng d  a0141-813000aInhibition of amyloid β1-42 peptide aggregation by newly designed cyclometallated palladium complexes0 aInhibition of amyloid β142 peptide aggregation by newly designed  cSEP   a1258470 v2483 a<p>
	Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L-1)Cl] Pd-1, [Pd(L-2)Cl](Pd-2), and [Pd(L-3)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and A beta(1-42) peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd -3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while am-yloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-beta peptides significantly reduced the pro-duction of ordered beta-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.</p>
10aA beta(1-42) peptide10aAggregation and molecular docking10aPalladium complex1 aSaini, Rahul1 aNavale, Govinda, R.1 aSingh, Sain1 aSingh, Haobam, Kisan1 aChauhan, Rahul1 aAgrawal, Sonia1 aSarkar, Dhiman1 aSarma, Manabendra1 aGhosh, Kaushik  uhttps://library.ncl.res.in/content/inhibition-amyloid-%CE%B21-42-peptide-aggregation-newly-designed-cyclometallated-palladium