Browsing by Author "D. R. Sharma"

Now showing 1 - 4 of 4

A Step Towards Development and Bio-evaluation of a Novel Radio-ligand 99mTc-CYX-DTPA Targeting Sigma 2 Receptors
(Bentham Science Publishers, 2025) Ritika Chaudhary; Shubhra Chaturvedi; Divya Gautam; Vishakha Chaudhary; D. R. Sharma; Presenjit; Aastha Garg; Madhu Chopra; Anil Kumar Mishra
Introduction: Development of theranostics agents targeted towards particular receptors can effectively help in the management of cancer. The overexpression of the sigma-2 receptor (S2R) in tumors establishes it as a prominent biomarker for cancer cells. Methods: Radiotheranostics rely on the design of specific molecules having versatility in applications of diagnosis and therapy by merely changing the radioisotope. We have designed a novel radiotheranostic S2R-targeted ligand using cyclohexylpiperazine and performed docking studies to narrow down the potential efficacious ligand. The potential molecule with G-score = -7.0 kcal/mol, was then synthesized using a three steps reaction including conjugation of 2-(4-cyclohexylpiperazine-1-yl)ethyl(CYX) with DTPA chelator. Subsequently, the molecule has been radiolabelled with 99mTc using stannous chloride as a reducing agent, and a radiolabellieng efficiency of 95.0 ± 0.59% for 99mTc-CYX-DTPA. As proof of concept, the molecule has been evaluated for its binding affinity and specificity using sigma receptors isolated from the liver membrane homogenates of mice. The binding affinity was found to be Kd = 12.84 ± 0.395 nM; Bmax = 0.5258 ± 0.001 fmol/mg, indicating a high affinity for the receptors. Results: In addition, the molecule was also assessed for biocompatibility using haemolysis analysis and cytotoxicity on HEK cells and MDA-MB-23, wherein the molecule showed no significant cytotoxicity up to 72 h on HEK cells and 32.42% cytotoxicity on MDA-MB-231 cells. Conclusion: The future work will concentrate on the demonstration of in vivo targeting and site-specific accumulation of the molecule along with its suitability for theranostics applications. © 2025 Bentham Science Publishers.
Homology modeling, molecular docking and MD simulations study of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives as sigma-2 receptor ligands
(Taylor and Francis Ltd., 2025) Vishakha Chaudhary; Shubhra Chaturvedi; Anju Wadhwa; Presenjit Verma; Divya Gautam; D. R. Sharma; Aastha Garg; Vishal Singh; Rupesh Kumar; Anil Kumar Mishra
The sigma-2 receptor has gathered attention as a promising target for cancer diagnosis and therapy since biochemical studies have evidenced the presence of the receptor in highly proliferating tumor cells. Computational drug design can help create targeted ligands against sigma-2, but a three-dimensional receptor structure is required as input. This study aims to develop a homology model of the human sigma-2 receptor. The template protein bovine sigma-2 (7m93) was aligned with the query sequence (Q5BJF2) to generate five models. These models were screened using potential energy parameters and molecular dynamics, with the model having the lowest energy and maximum stability being validated using stereo chemical parameters. The accepted model had 95.9% residues in allowed regions of the Ramachandran plot and an overall quality factor of 87.2611%. The model was tested using correlation analysis (R2= 0.744) of docking score and literature values of pKi. In addition, the model is used to understand the binding pattern of emerging selective 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline scaffold-based derivatives for designing ligands. The molecular dynamics studies of the model and ligand-bound model were performed for 100 ns to study the stability of the complexes, and the interactions compared with the known antagonist of sigma 2. © 2025 DRDO, India (previous affiliation). Published by Informa UK Limited, trading as Taylor & Francis Group.
Oxidase-Like Nanozyme Activity of Ultrathin Copper Metal–Organic Framework Nanosheets With High Specificity for Catechol Oxidation
(John Wiley and Sons Inc, 2025) Ajit Kumar Kumar Singh; D. R. Sharma; Devesh Kumar Singh; Sonu Sarraf; Aviru Kumar Basu; Vellaichamy Ganesan; Avishek Saha; Arindam Indra
In nature, catechol oxidase catalyzes the oxidation of o-diphenol to o-quinone to produce a series of highly important polyphenolic natural products. Although mimicking the functionality of natural enzyme using a nanozyme was found to be beneficial, attaining a high specificity is challenging. Herein, we have explored the thickness-dependent oxidase activity and specificity of Cu-metal-organic framework (MOF) nanosheets. The unique synthetic method offers control over the thickness of the Cu-MOF nanosheets. The ultrathin (4 nm) Cu-MOF (Cu-UMOF) nanosheets as an oxidase nanozyme exhibit high specificity for catechol oxidation without having any peroxidase activity. Interestingly, the thicker (20–30 nm) Cu-MOF nanosheets showed poor catechol oxidase and peroxidase activity. The binuclear Cu-center, coordinative, and electronic unsaturation tuned electronic structure in Cu-UMOF, resulting in higher specificity for catechol oxidation than thicker Cu-MOF. © 2024 Wiley-VCH GmbH.
Sigma-2 receptor-targeted functionalized carbon dots enable selective Fe3+detection and cellular imaging
(Royal Society of Chemistry, 2025) Divya Gautam; Ritika Chaudhary; D. R. Sharma; Vishakha Chaudhary; Shashikant; Shubhra Chaturvedi; Raj Kumar Dutta
Photoluminescent nitrogen doped carbon dots bearing a sigma-2 receptor pharmacophore (N-CDISQ) were synthesized and validated for in vitro biosensing of Fe3+. N-CDISQ exhibited intense blue photoluminescence at λ = 450 nm when excited at λ = 350 nm. N-CDISQ also exhibited selective fluorescence quenching by Fe3+ ions in the presence of anions and biomolecules. Quantitative analysis of photoluminescence quenching followed Stern–Volmer kinetics with a linear response for Fe3+ (5–90 μM). The detection limit was estimated to be 4.13 μM. Mechanistic studies confirmed static quenching and the involvement of interactions between Fe3+ and isoquinoline in the carbon dots. N-CDISQ demonstrated good biocompatibility, with cell viability above 80% after a 48-h treatment with concentrations up to 100 μM. Negligible erythrocyte rupture was observed in the haemolysis assay. Cellular imaging experiments demonstrated the bio-sensing capability of N-CDISQ to visualize Fe3+ ions within cells. The synthesized N-CDISQ represents a novel class of nitrogen-doped carbon dot-based fluorescent probes with dual functionality for quantitative Fe3+ analysis and cellular imaging. This journal is © The Royal Society of Chemistry, 2025