Vipin A. Nair

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an Aβ42-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated Aβ42-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through π–π stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski’s and Veber’s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD.

This study details the design, synthesis, and evaluation of a novel series of fourteen 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrid compounds. The primary objective was to investigate their potential as antimicrobial agents and assess their cytotoxicity. A systematic approach combining in silico screening and experimental validation was employed. The initial in silico analysis, using SwissADME, identified compounds with favorable drug-like properties. Subsequently, all fourteen compounds were synthesized and characterized using various spectroscopic methods. Their antibacterial efficacy was evaluated in vitro against Gram-negative (Klebsiella aerogenes) and Gram-positive (Enterococcus sp.) bacteria through growth kinetics and colony-forming unit (CFU) assays. Cytotoxicity was assessed using MTT assays on HEK (human embryonic kidney) cell lines. The compound, 2-((1H-1,2,4-triazol-3-yl)thio)-N′-(2-fluorobenzylidene)-N-phenylacetohydrazide emerged as the most promising candidate, demonstrating broad-spectrum antibacterial activity. These findings highlight the potential of 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrids as a scaffold for developing new antimicrobial agents. Furthermore, this study suggests possible environmental applications for these compounds in antimicrobial resistance (AMR) management.

Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability and neuronal loss. This review explores the contrasting role of OS in cancer stem cells (CSCs) and NDDs. Elevated levels of reactive oxygen species (ROS) contribute to genomic instability and promote tumor initiation and progression in CSCs, while in NDDs such as Alzheimer’s and Parkinson’s disease, OS accelerates neuronal death and impairs cellular repair mechanisms. Both scenarios involve disruption of the delicate balance between pro-oxidant and antioxidant systems, which leads to chronic oxidative stress. Notably, CSCs and neurons display alterations in redox-sensitive signaling pathways, including Nrf2 and NF-κB, which influence cell survival, proliferation, and differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function in CSCs supports adaptability and survival, whereas impairments in neurons heighten vulnerability. Understanding these common mechanisms of OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, and potentially mitigating or preventing both cancer and NDDs.