A5022795932- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- Genomics and Chromatin Dynamics
- Computational Drug Discovery Methods
- Quinazolinone synthesis and applications
- Molecular Sensors and Ion Detection
- Advanced biosensing and bioanalysis techniques
- Tuberculosis Research and Epidemiology
- Histone Deacetylase Inhibitors Research
- Luminescence and Fluorescent Materials
- Cancer, Hypoxia, and Metabolism
- Genetics and Neurodevelopmental Disorders
- HIV Research and Treatment
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Synthesis and bioactivity of alkaloids
- Chemical synthesis and alkaloids
- Alzheimer's disease research and treatments
- Nanoparticle-Based Drug Delivery
- RNA Interference and Gene Delivery
- Sulfur-Based Synthesis Techniques
- MicroRNA in disease regulation
- Nanoplatforms for cancer theranostics
- Cyclopropane Reaction Mechanisms
- Enzyme Catalysis and Immobilization
National Institute of Technology Durgapur
2019-2025
Texas A&M University
2018-2019
Indian Institute of Technology Kharagpur
2010-2015
Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we show the upregulation G9a and H3K9me2 in brains AD patients. Interestingly, treatment with inhibitor (G9ai) SAMP8 mice reversed high levels rescued cognitive decline. A transcriptional profile analysis after G9ai revealed increased gene expression glia maturation factor β (GMFB) mice. Besides, ChIP-seq inhibition showed enrichment promoters associated neural functions. We observed induction...
ABSTRACT This review provides a comprehensive overview of the role G9a/EHMT2, focusing on its structure and exploring impact pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into advancements design synthesis G9a/EHMT2 inhibitors, which hold promise not only as treatment for neurodegeneration diseases but also other conditions, such cancer malaria. Besides, presented discovery dual therapeutic approaches based G9a different epigenetic enzymes...
Protein arginylation mediated by arginyltransferase 1 is a crucial regulator of cellular processes in eukaryotes affecting protein stability, function, and interaction with other macromolecules. This enzyme its targets are immense interest for modulating diseased states like obesity cancer. Despite being an important target molecule, no highly potent drug against this exists. Therefore, study focuses on discovering potential inhibitors human computational approaches where screening over...
We report for the first time an organic nanoparticle based nuclear-targeted photoresponsive drug delivery system (DDS) regulated anticancer release. Acridin-9-methanol fluorescent nanoparticles used in this DDS performed three important roles: (i) ″nuclear-targeted nanocarrier″ delivery, (ii) ″phototrigger″ release, and (iii) chromophore cell imaging. In vitro biological studies reveal acridin-9-methanol of ~60 nm size to be very efficient delivering chlorambucil into target nucleus, killing...
JOURNAL/nrgr/04.03/01300535-202411000-00033/figure1/v/2024-04-10T160327Z/r/image-tiff Dysregulation of G9a, a histone-lysine N-methyltransferase, has been observed in Alzheimer’s disease and correlated with increased levels chronic inflammation oxidative stress. Likewise, microRNAs are involved many biological processes diseases playing key role pathogenesis, especially multifactorial such as disease. Therefore, our aim to provide partial insights into the interconnection between microRNAs,...
The genomic DNA of eukaryotic cells exists in the form chromatin, structure which controls biochemical accessibility underlying to effector proteins. In order gain an depth molecular understanding how chromatin regulates repair, detailed vitro and biophysical studies are required. However, because challenges associated with reconstituting nucleosome arrays containing site-specifically positioned modifications, such have been limited use mono- dinucleosomes as model substrates, incapable...
Abstract Despite recent evidence suggesting that histone lysine acetylation contributes to base excision repair (BER) in cells, their exact mechanistic role remains unclear. In order examine the influence of on initial steps BER, we assembled nucleosome arrays consisting homogeneously acetylated H3 (H3K18 and H3K27) measured a site-specifically positioned 2′-deoxyuridine (dU) residue by uracil DNA glycosylase (UDG) apurinic/apyrimidinic endonuclease 1 (APE1). We find H3K18ac H3K27ac...
A naphthalene-based azo armed molecular derivative was synthesized for sensing of Al 3+ and cell imaging studies. The fluorescence enhancement is caused by restricted CN isomerization, CHEF on, PET-off processes.
Although a functional relationship between active DNA demethylation and chromatin structure is often implied, direct experimental evidence lacking. We investigated the thymine glycosylase (TDG) using chemically defined nucleosome arrays containing site-specifically positioned 5-formylcytosine (5fC) residues. show that extent of array compaction, as well positioning, dramatically influence ability TDG to excise 5fC from DNA, indicating likely key determinant whether removed genome or retained...
We report the design and synthesis of triazole-polyphenol hybrid compounds 1 2 as inhibitors FabG4 (Rv0242c) enzyme Mycobacterium tuberculosis for first time. A major advance in this field occurred only a couple years ago with X-ray crystal structure FabG4, which has helped us to these by computational fragment-based drug (FBDD) approach. Compound shown competitive inhibition an constant (Ki) value 3.97 ± 0.02 μM. On other hand, compound been found be mixed type inhibitor Ki 0.88 0.01...
A newsworthy class of carboxylate esters based on the (benzo[a]acridin-12-yl)methyl (BAM) chromophore has been shown to perform dual functions as a "pH sensitive fluorescent probe" and "phototrigger" for acids. The photophysical properties all BAM ester conjugates were investigated found be highly solvent polarity, H-bonding capability pH environment. On irradiation using UV light (≥410 nm), underwent heterolytic cleavage C–O bonds resulting in efficient release carboxylic amino...
The G9a, Lysine Methyltransferase that methylates the histone 3 lysine 9 (H3K9) of nucleosome, is an excellent epigenetic target having no clinically passed inhibitor currently owing to adverse in vivo ADMET toxicities. In this work, we have carried out detailed computational investigations find novel and safer lead against using advanced D QSAR pharmacophore screening databases containing more than 400000 entrees natural compounds. was conducted at different levels increasing stringencies...
AbstractAbstractHerein, we report a blended ligand and structure-based pharmacophore screening approach to identify new natural leads against the Protein Lysine Methyltransferase 2 (EHMT2/G9a). The EHMT2/G9a has been associated with Cancer, Alzheimer's, aging is considered an emerging drug target having no clinically passed inhibitor. Purposefully, developed ligand-based (Pharmacophore-L) based on common features of known inhibitors (Pharmacophore-S) interaction profile available crystal...
Herein, we report for the first time G9a/EHMT2 inhibition and anti-Alzheimer's activities of drug raltitrexed. G9a is a lysine methyltransferase that mainly dimethylates H3K9 chromatin, which triggers repression genes epigenetically, leading to various diseased conditions, including Alzheimer's disease (AD). First, demonstrate raltitrexed inhibits at 120 nM. Moreover, lowers total H3K9me2/H3K9 levels in AD transgenic C. elegans CL2006 worms, indicating targets directly. As toxicity...
The regioselectivity of hydrolysis by Amano lipase (AK lipase) from Pseudomonas fluorescens aryl naphthalene 4′,7-diacetates 1a–c prepared the Garratt–Braverman cyclization bis-propargyl sulfones, ethers and sulfonamides acetylation corresponding diol 2a–c were studied. In all these cases, selectivity both excellent. However, pattern was found to be dependent upon nature fused heterocyclic ring, namely, dihydrothiophene dioxide (sulfolene), dihydrofuran (phthalan) or dihydro isoindole...
Drug discovery is still behind in the race compared to vaccine fighting COVID-19. In this study, we have selected 41 quinazoline alkaloids from two natural product databases create an adequate library and performed detailed computational studies against main protease ([Formula: see text]) of SARS-CoV-2 using reference compounds, namely famotidine X77. The screening was carried out by blending rigid docking pharmacokinetic analysis that resulted nine as initial leads [Formula: text]. These...
Drug discovery is still behind in the race compared to vaccine fighting COVID-19. Recently, a few alkaloids from traditional Indian medicinal plant, Vasaka (Justicia adhatoda), have been linked computationally main protease (Mpro) of SARS_CoV_2. To expand knowledge and for further investigation, we selected 41 quinazoline two natural product databases create an adequate library performed detailed computational studies against The screening was carried out through blending rigid docking...