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This study investigates the potential of click chemistry for the development of novel anti-tuberculosis agents. A targeted library of 1,4-dihydropyridine-1,2,3-triazole conjugates was synthesized and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Ra using the resazurin microtiter assay (REMA). Among the synthesized derivatives, compounds J10, J11, J14, J22 and J23 demonstrated significant antimycobacterial activity. These compounds exhibited low MIC values ranging from 6.24 to 6.64 µg mL-1, highlighting their promising potential as lead compounds for further developing novel tuberculosis therapeutics. In addition to the promising in vitro activity, structure-activity relationship (SAR) analysis revealed that electron-withdrawing groups on the aryl-substituted ring of the dihydropyridines (J10-J24), a triazole with an unsubstituted aryl ring or with electron-donating groups (methyl or methoxy), and a geminal dimethyl group are essential structural features for the observed antitubercular activity. Furthermore, in silico ADME (absorption, distribution, metabolism, and excretion) parameters and pharmacokinetic studies supported the potential of these conjugates for oral bioavailability. These findings collectively highlight the 1,4-dihydropyridine-1,2,3-triazole scaffold as a promising platform for developing novel orally active anti-tuberculosis drugs.
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Plastics are ubiquitous in today's lifestyle, and their indiscriminate use has led to the accumulation of plastic waste in landfills and oceans. The waste accumulates and breaks into micro-particles that enter the food chain, causing severe threats to human health, wildlife, and the ecosystem. Environment-friendly and bio-based degradable materials offer a sustainable alternative to the vastly used synthetic materials. Here, a polylactic acid and carbon nanofiber-based membrane and a paper-based colorimetric sensor have been developed. The membrane had a surface area of 3.02 m2 g-1 and a pore size of 18.77 nm. The pores were evenly distributed with a pore volume of 0.0137 cm3 g-1. The membrane was evaluated in accordance with OECD guidelines and was found to be safe for tested aquatic and terrestrial models. The activated PLA-CNF membrane was further used as a bio-based electrode for the electrochemical detection of nitrates (NO3-) in water samples with a detection limit of 0.046 ppm and sensitivity of 1.69 × 10-4 A ppm-1 mm-2, whereas the developed paper-based colorimetric sensor had a detection limit of 156 ppm for NO3-. This study presents an environment-friendly, low-carbon footprint disposable material for sensing applications as a sustainable alternative to plastics.
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Carbono , Colorimetría , Nanofibras , Nitratos , Papel , Poliésteres , Nanofibras/química , Colorimetría/métodos , Colorimetría/instrumentación , Nitratos/análisis , Nitratos/química , Poliésteres/química , Carbono/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Límite de Detección , Contaminantes Químicos del Agua/análisis , Conductividad Eléctrica , Membranas ArtificialesRESUMEN
Natural and synthetic dyes are added to different food commodities to enhance their appearance and acceptance by consumers. Acute and chronic exposure owing to the consumption of non-permitted dyes may lead to health concerns such as allergic reactions, eczema, and asthma. 4-(Dimethylamino)azobenzene (4-DMAAB) is a non-permitted dye that has been reported in adulterated mustard oil. Consumption of 4-DMAAB poses severe risks due to its mutagenic and carcinogenic properties. Several sensitive methods such as FT-NIR, FT-MIR and SERS are available for the detection of 4-DMAAB. Here, a spectrophotometric method was developed for the detection of 4-DMAAB. The developed method was translated to a point-of-test paper-based, chromogenic strip which showed a detection limit of 0.025 mM for 4-DMAAB. Also, an electrochemical sensor was developed by electro-depositing the test solution on a screen-printed electrode. The electrochemical sensor showed an LOD of 0.027 ± 0.008 mM with recovery in the range of 91-107% of 4-DMAAB. Oil samples collected from the market were processed by liquid-liquid extraction and the content of 4-DMAAB was assessed. The developed point-of-use sensors for the detection of 4-DMAAB have potential for use by the consumers, food industry and regulatory agencies for on-site analysis and assuring the quality of edible oils.
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Compuestos Azo , Colorantes , Metacrilatos , Límite de DetecciónRESUMEN
Understanding the role of interparticle interactions in jamming phenomena is essential for gaining insights into the intriguing glass transition behavior observed in atomic and molecular systems. In this study, we investigate the jamming behavior of colloids with tunable interparticle interactions during evaporation-induced assembly (EIA). By manipulating the interaction among charged colloids using cationic polyethyleneimine (PEI) through electro-sorption and subsequent free polymer induced repulsion, we observe distinct jamming behavior in silica colloids during EIA, depending on the interparticle interactions. Silica colloids with strong repulsive interactions exhibit a repulsive colloidal glass state with a volume fraction of silica colloids in supraparticle Ï â¼ 0.70. On the other hand, PEI-mediated attractive interactions among silica colloids lead to an attractive colloidal glass phase with a significantly lower Ï â¼ 0.43. Free polymer induced repulsion of colloids at higher PEI concentration once again results in a repulsive glassy state with Ï â¼ 0.61. Furthermore, we revealed that interparticle interactions not only influence the jamming behavior but also play a significant role in shaping the morphology of self-assembled structures during EIA, and the assembled structure undergoes a morphological reentrant transition from a doughnut-like shape to a spherical form and again back to a doughnut-like configuration. Jamming-dependent evolution of micropores and dynamics of the confined PEI have been probed using positron annihilation lifetime spectroscopy (PALS) and broadband dielectric spectroscopy (BDS). PALS reveals distinct variations in the micropores of the supraparticles with different PEI loadings, confirming the impact of jamming on the evolution of the micropores within the supraparticles. BDS measurements uncover non-monotonic dynamics of PEI molecules confined in the evolved pore network. It is revealed that the reentrant jamming behavior of colloids, modulated by PEI, holds profound significance for the long-term stability of supraparticles.
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Hydrogen peroxide (H2O2) is commonly used as a preservative, disinfectant, bleach, and oxidizing agent. The prolonged consumption of H2O2 adulterated milk is harmful to human health when consumed in the diet. Exposure to H2O2 can lead to oxidative stress, cell damage and tissue injury. Due to the potential adverse effects, the use of hydrogen peroxide is regulated in certain applications, such as in food, water treatment plants and medical products. Several methods are available for the detection of H2O2 in various matrices. Here, a method and QR code-integrated chromogenic paper strip for the detection of H2O2 in aqueous samples has been developed. The spectrophotometric method showed an LOD and LOQ of 0.00087 ± 8.70 ×10-5% (v/v) and 0.0037 ± 0.0003% (v/v), respectively. The paper-based chromogenic strip prepared by immobilizing recognition solution onto a QR code was able to detect 0.0005% v/v of H2O2 in aqueous samples. The QR integrated chromogenic paper strip sensors can serve as a useful tool for consumers, regulatory agencies, and the food industry to assess food quality and authenticity.
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Peróxido de Hidrógeno , Oxidantes , Humanos , Espectrofotometría , Estrés OxidativoRESUMEN
Post-translational modifications guide the functional diversity and identity of proteins. Phosphorylation is one such post-translational modification that has been reported in pathological proteins related to various neurodegenerative disorders such as α-synuclein (α-syn) phosphorylation in Parkinson's disease and other synucleinopathies. In α-syn, the phosphorylation has mostly been observed at S129; however, the occurrence of other serine modifications at S9, S42, and S87 is partially explored. In pathogenic conditions, where α-syn is phosphorylated by complex kinase pathways, multi-site modifications may happen and alter the mechanism of α-syn aggregation. Here, using Polo-like kinase 2 and G-protein coupled receptor kinase 4, the in vitro phosphorylation of α-syn was performed, which revealed multi-serine phosphorylation. Mass spectrometry with customized proteolytic digestion showed prominent phosphorylation at S129 and modifications at S87 and S42 with PLK2 and S87 with GRK4. The phosphorylation at the identified serine residues was further validated with NMR and western blotting. Multi-serine phosphorylation aggravates the aggregation potential of monomeric α-syn, seeding capacity, and cytotoxicity in the SH-SY5Y cell line. This study proposes evidence for in vitro multi-site phosphorylation and its significance in α-syn aggregation, toxicity, and related pathogenesis.
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Neuroblastoma , Enfermedad de Parkinson , Humanos , alfa-Sinucleína/metabolismo , Fosforilación , Serina/metabolismo , Enfermedad de Parkinson/metabolismoRESUMEN
Small molecules are being explored intensively for their applications as therapeutic molecules in the management of metabolic and neurological disorders. The natural small molecules can inhibit protein aggregation and underlying cellular pathogenesis of neurodegenerative diseases involving multi-factorial mechanisms of action. Certain natural small molecular inhibitors of pathogenic protein aggregation are highly efficient and have shown promising therapeutic potential. In the present study, Shikonin (SHK), a natural plant-based naphthoquinone has been investigated for its aggregation inhibition activity against α-synuclein (α-syn) and the neuroprotective potential in Caenorhabditis elegans (C. elegans). SHK significantly inhibited aggregation of α-syn at sub-stochiometric concentrations, delayed the linear lag phase and growth kinetics of seeded and unseeded α-syn aggregation. The binding of SHK to the C-terminus of α-syn maintained α-helical and disordered secondary structures with reduced beta-sheet content and complexity of aggregates. Further, in C. elegans transgenic PD models, SHK significantly reduced α-syn aggregation, improved locomotor activity and prevented dopaminergic (DA) neuronal degeneration, indicating the neuroprotective role of SHK. The present study highlights the potential of natural small molecules in the prevention of protein aggregation that may further be explored for their therapeutic efficacy in the management of protein aggregation and neurodegenerative diseases.
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Bioelectrodes with low carbon footprint can provide an innovative solution to the surmounting levels of e-waste. Biodegradable polymers offer green and sustainable alternatives to synthetic materials. Here, a chitosan-carbon nanofiber (CNF) based membrane has been developed and functionalized for electrochemical sensing application. The surface characterization of the membrane revealed crystalline structure with uniform particle distribution, and surface area of 25.52 m2/g and pore volume of 0.0233 cm3/g. The membrane was functionalized to develop a bioelectrode for the detection of exogenous oxytocin in milk. Electrochemical impedance spectroscopy was employed to determine oxytocin in a linear concentration range of 10 to 105 ng/mL. The developed bioelectrode showed an LOD of 24.98 ± 11.37 pg/mL and sensitivity of 2.77 × 10-10 Ω / log ng mL-1/mm2 for oxytocin in milk samples with 90.85-113.34 percent recovery. The chitosan-CNF membrane is ecologically safe and opens new avenues for environment-friendly disposable materials for sensing applications.
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Técnicas Biosensibles , Quitosano , Nanofibras , Carbono/química , Quitosano/química , Oxitocina/química , Electrodos , Técnicas Biosensibles/métodosRESUMEN
The rapidly growing electronic and plastic waste has become a global environmental concern. Developing advanced and environmentally safe agro-based materials is an emerging field with an enormous potential for applications in sensors and devices. Here, an agro-based material as membrane has been developed by incorporating tapioca starch and banana peel powder in polylactic acid, with uniform dispersibility and amorphous nature. The material was used for the development of electrochemical sensor for S-gene of SARS-CoV-2. Further, the membrane was used for the development of a non-invasive, colorimetric skin patch for the detection of glucose and a sensor for the assessment of fruit juice quality. Using OECD-recommended model systems, the developed membrane was found to be non-toxic towards aquatic and terrestrial non-target organisms. The developed conductive material opens new avenues in various electrochemical, analytical, and biological applications.
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Técnicas Biosensibles , COVID-19 , Manihot , Musa , Musa/química , Colorimetría , COVID-19/diagnóstico , SARS-CoV-2 , Almidón/químicaRESUMEN
Bismuth vanadate (BiVO4) is a promising photoactive material for the design of photoelectrochemical (PEC) analytical devices for the non-enzymatic detection of glucose. In this work, un-doped and La/Ce/Zr doped BiVO4 photo anodes were developed by spray pyrolysis coating to generate unique 2D hierarchical architectures using the facile ultrasonic spray coating technique without any complex pre or post-treatment. The influence of different dopants on the morphology and photoelectrochemical activity of BiVO4 coatings was investigated. X-ray diffraction, scanning electron microscopy, UV-vis optical absorbance, and positron annihilation techniques were used to evaluate the structure, defects, and optical properties of BiVO4 films. DFT simulation confirmed the Zr doping induced band gap reduction in the BiVO4 lattice. The Zr doping on the Bi site in BiVO4 lattice provided significantly low Bi and V-based defect density and a higher bulk diffusion length of charge pairs (4 times that of pristine) as well as charge transfer efficiency and this led to the foremost photocurrent for water splitting. The Zr-doped BiVO4 photo anode showed remarkable sensitivity in glucose sensing. The sensitivity and limit of detection of the Zr-doped BiVO4 PEC device towards glucose were 0.14 mA cm-2 mM-1 and 1.22 µM, respectively, in the concentration range of 1-7 mM. The system showed sensitive detection of glucose in blood serum. This is the first time that a 2D morphology electrode design consisting of Zr-doped BiVO4, which leads to exceptionally high sensitivity for glucose sensing, has been reported.
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Glucosa , Suero , Vanadatos , DifusiónRESUMEN
The use of biopolymers is gaining momentum owing to their compatibility with various food commodities and acceptability by the industry and consumers. Biopolymers integrated with natural pigments can be used for assessing the quality of perishable packaged food products. Here, a biodegradable composite membrane of starch and chitosan, integrated with anthocyanin has been developed. The chromogenic response of the developed biocomposite membrane was used to assess spoilage in milk. The surface roughness recorded using atomic force microscopy and scanning electron microscopy showed smooth membrane surface, and a pore size 4.21 nm was determined by Brunauer-Emmett-Teller analysis. The water vapour transmissibility of the membrane was 4.616E-09 and 1.147E-08 g/h Pa.mm and water solubility was 5.6 and 5.8 % at 25 and 37 â, respectively, indicating high water resistance and low vapour transmission rate. The developed biocomposite membrane offers an environment friendly substrate for biosensing with a promising potential in smart food-packaging applications.
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Quitosano , Vapor , Antocianinas , Embalaje de Alimentos , Almidón , Calidad de los AlimentosRESUMEN
The accumulation of protein aggregates as intracellular inclusions interferes with cellular protein homeostasis leading to protein aggregation diseases. Protein aggregation results in the formation of several protein conformers including oligomers and fibrils, where each conformer has its own structural characteristic and proteotoxic potential. The present study explores the effect of alpha-synuclein (α-syn) conformers on the activity and spontaneous refolding of firefly luciferase. Of the different conformers, α-syn monomers delayed the inactivation of luciferase under thermal stress conditions and enhanced the spontaneous refolding of luciferase. In contrast, the α-syn oligomers and fibrils adversely affected luciferase activity and refolding, where the oligomers inhibited spontaneous refolding, whereas a pronounced effect on the inactivation of native luciferase was observed in the case of fibrils. These results indicate that the oligomers and fibrils of α-syn interfere with the refolding of luciferase and promote its misfolding and aggregation. The study reveals the differential propensities of various conformers of a pathologically relevant protein in causing inactivation, structural modifications and misfolding of other proteins, consequently resulting in altered protein homeostasis.
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alfa-Sinucleína , Humanos , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/metabolismo , Agregado de Proteínas , Pliegue de Proteína , Luciérnagas , Luciferasas/química , Luciferasas/metabolismoRESUMEN
Consistently emerging variants and the life-threatening consequences of SARS-CoV-2 have prompted worldwide concern about human health, necessitating rapid and accurate point-of-care diagnostics to limit the spread of COVID-19. Still, However, the availability of such diagnostics for COVID-19 remains a major rate-limiting factor in containing the outbreaks. Apart from the conventional reverse transcription polymerase chain reaction, loop-mediated isothermal amplification-based (LAMP) assays have emerged as rapid and efficient systems to detect COVID-19. The present study aims to develop RT-LAMP-based assay system for detecting multiple targets in N, ORF1ab, E, and S genes of the SARS-CoV-2 genome, where the end-products were quantified using spectrophotometry, paper-based lateral-flow devices, and electrochemical sensors. The spectrophotometric method shows a LOD of 10 agµL-1 for N, ORF1ab, E genes and 100 agµL-1 for S gene in SARS-CoV-2. The developed lateral-flow devices showed an LOD of 10 agµL-1 for all four gene targets in SARS-CoV-2. An electrochemical sensor developed for N-gene showed an LOD and E-strip sensitivity of log 1.79 ± 0.427 pgµL-1 and log 0.067 µA/pg µL-1/mm2, respectively. The developed assay systems were validated with the clinical samples from COVID-19 outbreaks in 2020 and 2021. This multigene target approach can effectively detect emerging COVID-19 variants using combination of various analytical techniques at testing facilities and in point-of-care settings.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sensibilidad y Especificidad , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , ARN Viral/genéticaRESUMEN
Engineered nanoparticles (ENPs) are artificially synthesized particles with unique physicochemical properties. ENPs are being extensively used in several consumer items, elevating the probability of ENP exposure to biological systems. ENPs interact with various biomolecules like lipids, proteins, nucleic acids, where proteins are most susceptible. The ENP-protein interactions are mostly studied for corona formation and its effect on the bio-reactivity of ENPs, however, an in-depth understanding of subsequent interactive effects on proteins, such as alterations in their structure, conformation, free energy, and folding is still required. The present review focuses on ENP-protein interactions and the subsequent effects on protein structure and function followed by the therapeutic potential of ENPs for protein misfolding diseases.
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The quality of packaged fruit juices is affected during their processing, packaging and storage that might cause deteriorative biological, chemical and physical alterations. Consumption of spoiled juices, either from biological or non-biological sources can pose a potential health hazard for the consumers. Sensitive and reliable methods are required to ensure the quality of fruit juices. Standard analytical methods such as chromatography, spectrophotometry, electrophoresis and titration, that require sophisticated equipment and expertise, are traditionally used to assess the quality of fruit juices. Using biosensors, that are simple, portable and rapid presents a promising alternative to the tedious analytical methods for the detection of various degradation and spoilage indicators formed in the packaged fruit juices. Here, we review the challenges in maintaining the quality of fruit juices and the recent developments in techniques and biosensors for quick analysis of fruit juice components.
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Técnicas Biosensibles , Jugos de Frutas y Vegetales , Bebidas/análisis , Frutas/química , Jugos de Frutas y Vegetales/análisis , EspectrofotometríaRESUMEN
Improper storage and transportation of non-alcoholic beverages can, over longer periods, induce Maillard reaction, degrading nutritional components and generating genotoxic and carcinogenic by-products such as furfural and 5-hydroxymethylfurfural (HMF), rendering products unsafe for human consumption. Here, we describe a rapid quantitative solution-based method and test-strips for detection of furfural and HMF. The standard spectroscopic method indicated an LOD of 0.006⯱â¯0.003% (v/v) and 0.005⯱â¯0.002% (v/v) for furfural and HMF, respectively in fruit juice samples. The novel chromogenic test-strip has sensitivity of 0.008% (v/v) and 0.004% (v/v) for furfural and HMF, respectively in the same samples of fruit juice. Thus, the developed method and test-strips were specific for furfural and HMF and can be used to help ensure food safety and quality in various industrial applications.
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Jugos de Frutas y Vegetales , Furaldehído , Bebidas/análisis , Furaldehído/análogos & derivados , Furaldehído/análisis , Humanos , Reacción de MaillardRESUMEN
The progression of plastic pollution is a global concern. "Reuse, reduce and recycle" offers a solution to the burdening issue, although not enough to curb the rampant use of plastics. Biodegradable plastics are gaining acceptability in agriculture and food packaging industries; nevertheless, they occupy a rather small section of the plastic market. This review summarizes recent advances in the development of biodegradable plastics and their safe degradation potentials. Here, biodegradable plastics have been categorized and technology and developments in the field of biopolymers, their applicability, degradation and role in sustainable development has been reviewed. Also, the use of natural polymers with improved mechanical and physical properties that brings them at par with their counterparts has been discussed. Biodegradable polymers add value to the industries that would help in achieving sustainable development and consequently reinforce green economy, reducing the burden of greenhouse gases in the environment and valorisation of waste biomass.
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Plásticos Biodegradables , Polímeros , Biodegradación Ambiental , Biopolímeros , Plásticos , ReciclajeRESUMEN
Enoyl-acyl carrier protein reductase (InhA) of type II fatty acid synthase system is involved in the synthesis of mycolic acids which is a major component of the bacterial cell wall. Since they are the key enzymes playing a very significant role in the FASII pathway of the bacterium. In this study, we have developed a workflow for identification of InhA inhibitors by utilizing in silico virtual screening approaches based on various machine learning algorithms followed by pharmacophore based virtual screening. The hits screened from the models were further subjected to molecular docking. Further, based on the XP docking score best twenty compounds were subjected to molecular dynamics study. Finally, nine compounds were shortlisted on the basis of best stable ligand RMSD, c-alpha RMSD, and RMSF plot for biological evaluation studies. Experimental validation of the shortlisted compounds identified one compound JFD01724 having potent inhibitory activity and was able to inhibit the growth of mycobacterium tuberculosis. Further medicinal chemistry efforts may help to improve the inhibitory potency of the identified compound.
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Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Modelos Moleculares , Mycobacterium tuberculosis/enzimología , Proteínas Bacterianas , Descubrimiento de Drogas , Ligandos , Aprendizaje Automático , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mycobacterium tuberculosis/efectos de los fármacosRESUMEN
Alkali metal (Na or K) doping in BiVO4 was examined systematically for enhancing bulk charge separation and transport in addition to improving charge transfer from the surface. The alkali metal-doped BiVO4 thin film photoanodes having nanostructured porous grain surface morphology exhibited better photocurrent density than pristine BiVO4. In particular, Na:BiVO4/Fe:Ni/Co-Pi photoanode showed a significantly improved photocurrent of 3.2 ± 0.15 mA·cm-2 in 0.1 M K2HPO4 electrolyte at 1.23 VRHE under 1 sun illumination. The depth-dependent Doppler broadening spectroscopy measurements confirmed the significant reduction in Bi- and V-based defect density with Na metal doping, and this led to a higher bulk diffusion length of charge pairs (four times that of the pristine one). Na doping led to reduced surface defects resulting in improved surface charge transfer based on cyclic voltammetry experiments. The density functional theory calculations confirmed the improved performance in Na-doped BiVO4 photoanodes achieved through interband formation and reduction in the band gap.
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Aggregation of α-synuclein (α-syn) is associated with the manifestation of various pathogenic synucleinopathies, including Parkinson's disease attributed to both genetic and environmental stress factors. The initial events triggering α-syn aggregation and disease initiation due to environmental stress factors are still largely unknown. Here, to understand the mechanism of misfolding and aggregation initiation, we induced α-syn aggregation with rotenone, an established chemical inducer of PD like symptoms. We found that rotenone accelerates the formation of structurally distinct oligomers and fibrils that act as templates and increase the formation of conformers capable of spreading to the neighboring neuronal cells. Molecular dynamics simulations and NMR studies revealed the involvement of NAC region and formation of helical conformations resulting in structural variations in oligomers and fibrils. These structural variations affect the cytotoxic potential of oligomers and fibrils, where, the beta sheet rich oligomers and fibrils alter the membrane potential of neuronal cells and lead to early apoptosis. Our results describe the initial mechanistic events in pathogenic protein aggregation, where initial structural alterations in response to external stress factors dictate the toxicity of resulting conformers. This information will further provide insights in the understanding of protein aggregation, disease progression and pathogenesis.