Applied Chemistry Department http://dspace.dtu.ac.in:8080/jspui/handle/repository/19775 2026-07-25T03:24:06Z 2026-07-25T03:24:06Z UPADHYAY, DHATRI RANI, ARCHNA (SUPERVISOR ) http://dspace.dtu.ac.in:8080/jspui/handle/repository/23046 2026-07-23T04:45:29Z 2026-06-01T00:00:00Z

Title: CHEMICAL AND BIOLOGICAL INVESTIGATION OF KEAP1–NRF2 PATHWAY AND ROLE OF SESAMIN IN OXIDATIVE STRESS AND AGEING Authors: UPADHYAY, DHATRI; RANI, ARCHNA (SUPERVISOR ) Abstract: The Kelch-like ECH-associated protein 1 and nuclear factor erythroid 2-related factor 2 (KEAP1–NRF2) signalling axis is the most critical and conserved cellular defence system against redox perturbations. Under basal conditions, NRF2 is constitutively ubiquitinated and targeted for proteasomal degradation through its interaction with KEAP1, a Cullin 3 based E3 ubiquitin ligase adaptor. Upon exposure to oxidative or electrophilic stimuli, cysteine residues within KEAP1 are covalently modified, disrupting its interaction with NRF2. Consequently, NRF2 escapes proteasomal degradation, translocate to the nucleus, and heterodimerizes with small musculoaponeurotic fibrosarcoma (sMAF) proteins to drive transcription of antioxidant response element (ARE)-dependent cytoprotective genes. Sesamin, a lipophilic lignan abundantly present in sesame seeds (Sesamum indicum), has emerged as a biologically significant natural compound with well documented antioxidant, anti-inflammatory, and neuroprotective properties. This activation then stimulates an increase in the amount of NRF2 transported into the nucleus, a decrease in the amount of KEAP1 in cells, and an increase in the number of ARE regulated cytoprotective genes expressed by the cell. The biological significance of the NRF2 pathway extends to multiple organ systems. With age, there is a decline in NRF2 activity resulting in the accelerated pace of cellular senescence, development of the senescence-associated secretory phenotype (SASP), neurodegeneration, sarcopenia, impaired lacrimal and salivary gland functioning, and hearing loss. Data from both in vitro and in vivo experimental settings establish that treating rats or providing a diet that includes components proven to restore NRF2 activity can lessen some of the effects associated with advanced age. Because of sesamin’s demonstrated ability to modulate NRF2, it is an attractive candidate for developing a natural therapeutic approach to counteract the effects of aging due to oxidative stress and neurodegeneration. This dissertation incorporates redox chemistry, molecular biology, and natural product pharmacology to present a complete view of the KEAP1–NRF2–sesamin axis and its role in maintaining healthy ageing.

2026-06-01T00:00:00Z ANJALI KHANEJA, YASH SRIVASTAVA, RICHA (SUPERVISOR) http://dspace.dtu.ac.in:8080/jspui/handle/repository/23045 2026-07-23T04:38:13Z 2026-06-01T00:00:00Z

Title: PYRIMIDINE ANALOGUES AS ANTI NEURO DEGENERATIVE AGENTS Authors: ANJALI; KHANEJA, YASH; SRIVASTAVA, RICHA (SUPERVISOR) Abstract: , Neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) altogether comprise one neurodegenerative mechanisms involved in the disease development. This dissertation attempts to investigate the possibility of using the pyrimidine derivatives as neuroprotective agents, particularly emphasizing on their polypharmacology profiles. Pyrimidine, a heteroaromatic compound with six members containing a nitrogen atom, is well known for its chemical diversity, brain penetration, favorable physiochemical properties, and ability to interact with different biological receptors related to neurodegeneration. Among the important pathologic processes that have been considered in this research project are aggregation of amyloid-β, tau protein hyperphosphorylation, neurotransmitter imbalance (cholinergic and dopaminergic systems), oxidative stress associated with monoamine oxidase B (MAO-B) and chronic neuroinflammation. A systematic SAR study was conducted with a view to finding out how structural variations in certain positions in the pyrimidine scaffold affected the enzymes' binding affinity, lipophilicity, selectivity towards various types of receptors and central nervous system penetration. Functional groups examined within the context of this work included amino groups, diamino groups, styryl groups and electron donating/withdrawing substituents as regards their effects on the inhibitory activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and monoamine oxidase B (MAO-B). Experimental work entailed in silico molecular docking of some selected pyrimidines against three neurodegeneration-related protein targets: monoamine oxidase B (PDB: 2BYB), acetyl-cholinesterase (PDB: 4BDT) and butyrylcholinesterase (PDB: 6QAB). In silico docking was done using recognized computational software, while docking scores were determined based on molecular interaction between the proteins and ligands. Among the selected pyrimidines, compound numbers 19 and 22 exhibited remarkable binding to MAO-B, while compounds 10 and 22 had favourable docking scores against acetylcholinesterase and butyryl-cholinesterase respectively. This study has established an excellent computational platform that will guide the future development of drugs based on pyrimidine compounds to target the highly complicated neurodegenerative pathways.

2026-06-01T00:00:00Z JAISWAL, KRITIKA Kumar, D. (SUPERVISOR) Gupta, R.K. (CO-SUPERVISOR) http://dspace.dtu.ac.in:8080/jspui/handle/repository/23041 2026-07-15T05:04:44Z 2026-06-01T00:00:00Z

Title: ELECTROCHEMICAL BIOSENSING PLATFORM UTILIZING GRAPHITIC CARBON NITRIDE-COPPER SULFIDE NANOHYBRID FOR SENSITIVE TRICHLORFON DETECTION Authors: JAISWAL, KRITIKA; Kumar, D. (SUPERVISOR); Gupta, R.K. (CO-SUPERVISOR) Abstract: Trichlorfon (TF) is considered the most frequently used organophosphorus compound among all compounds used for agricultural purposes. As such, TF can be quite effective in controlling insects that damage crops in several different ways. However, TF is toxic, and when individuals consume food contaminated with TF, it inhibits acetylcholinesterase, leading to a massive buildup of neurotransmitters at nerve synapses, ultimately disrupting normal nerve signal transmission and potentially causing severe neurological disorders. To address this problem, we have created a rapid, low-cost electrochemical biosensor using acetylcholinesterase (AChE) to detect the organophosphate pesticide (TF) via a g-C3N4/CuS-based nanocomposite. Electrostatic interactions between the g-C3N4/CuS nanocomposite enhance electron transfer to the electrode surface, thereby facilitating the covalent immobilization of AChE onto the electrode, with glutaraldehyde as a cross-linker to prevent enzyme leaching. Biosensor (AChE/g-C3N4/CuS/ITO) demonstrated an ultrahigh sensitivity toward TF over the linear range 0.1 pM - 1 µM. The developed biosensor showed stability, interference capability, good reproducibility and improved sensitivity. These characteristics enabled us to successfully detect TF in two real samples: apple and cucumber.

2026-06-01T00:00:00Z FATMA, FARHEEN GOYAL, SHAILY SANTHIYA, DEENAN (SUPERVISOR) http://dspace.dtu.ac.in:8080/jspui/handle/repository/23040 2026-07-13T04:42:57Z 2026-06-01T00:00:00Z

Title: VITAMIN-C TEMPLATED BIOACTIVE GLASS NANOPARTICLES AND THEIR INTEGRATION INTO METHYL CELLULOSE-PECTIN FILMS FOR BIOMEDICAL APPLICATIONS Authors: FATMA, FARHEEN; GOYAL, SHAILY; SANTHIYA, DEENAN (SUPERVISOR) Abstract: Bioactive glass has a phenomenal ability to interact when in contact with biological tissues and promote healing through controlled ion release. In this study, bioactive glass nanoparticles were synthesized using Vitamin C which acts as a natural template. The NPs were characterized by UV-Visible Spectroscopy to confirm the formation of glass network, Zetasizer analysis for the size and surface charge of the particle, Fourier Transform infrared spectroscopy to analyse its structural properties. Further, BGNPs were incorporated into films consisting of Methyl Cellulose and Pectin. In this film, glycerol was used as a plasticizing agent to reduce brittleness and boost the flexibility of the film. Methyl Cellulose provided mechanical strength to the film and enhanced its transparency while pectin provided gelling and antioxidant potential. The film was prepared with an aim to develop platform suitable for biomedical applications.

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