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There are no Food and Drug Administration‐approved drugs for treating noise‐induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM‐encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro‐computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained‐release and long‐term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug‐based treatment of NIHL. [ABSTRACT FROM AUTHOR]

In the present work, the chemical and electronic properties of a series of thiazole derivatives are presented by means of quantum chemical calculations. Solvation effects in different solvents are determined and for TH9 with acetonitrile the solvent energy is positive (120.80 kcal/mol) and for all other derivatives in different solvents, the solvent energy is less than 5 kcal/mol. Solvation free energies values suggest that chloroform and DMSO solvents may be better for the solubilization of thiazole. NLO and chemical properties are also found for all derivatives and compared. Biological activity is predicted and the binding affinity values from docking studies are reported along with amino acid interaction. [ABSTRACT FROM AUTHOR]

In this paper we report the synthesis, in‐silico and in‐vitro evaluations of a new series of benzothiazole linked triazole conjugates. The synthesized compounds have been evaluated as the inhibitor of cholinesterase enzymes using Ellman's method. The benzothiazole and triazole derivatives were synthesized separately and further combined through covalent amide bond linkage.The compounds showed good to excellent results towards butyryl cholinesterase (BuChE) inhibition. Docking studies revealed that the hydrophobic aromatic part of N‐benzothiazole binds to the PAS and the 1,2,4‐triazole residue binds to the CAS of BuChE. The in‐silico docking results for BuChE are consistent with the in‐vitro results. Also, the molecular dynamics simulation studies of the best docked molecule 8 a had shown similar binding stability as the reference drug donepezil. Good molecular interaction was also observed for acetylcholinesterase (AChE). The molecular modelling and evaluations against cholinesterase enzyme provided novel lead molecule which with further modifications in their structure have potential for the treatment of Alzheimer disease (AD) in future. [ABSTRACT FROM AUTHOR]