Browsing by Author "Divya Gautam"

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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.
Agent-based computational modeling of emergent collective intelligence
(Springer Verlag, 2009) Vivek Kumar Singh; Divya Gautam; Rishi Raj Singh; Ashok K. Gupta
Collective Intelligence is a form of intelligence which emerges out of collaboration and coordination of many individual agents. A group of actors performing simple behaviours and interacting with fellow group members & the environment often produce global behaviours which seems intelligent. Understanding the emergence of intelligent collective behaviours in social systems, such as norms & conventions, higher level organizations, collective wisdom and evolution of culture from simple and predictable local interactions; has been an important research question since decades. Agent-based modeling of complex social behaviours by simulating social units as agents and modeling their interactions; provides a new generative approach to understanding the dynamics of emergence of collective intelligence behaviours. In this paper, we have presented an analytical account of nature, form and dynamics of collective intelligence, followed by some of our experimental work on evolution of collective intelligence. The paper concludes with a short discussion of the results and relevant implications for designing systems for achieving desired collective intelligence. © 2009 Springer Berlin Heidelberg.
Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent
(Elsevier Ltd, 2024) Vishakha Chaudhary; Shubhra Chaturvedi; Anju Wadhwa; Ritika Chaudhary; Divya Gautam; Deepika Sharma; Rupesh Kumar; A.K. Mishra
Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging. © 2023 Elsevier Ltd
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.
Multi-agent based models of social contagion and emergent collective behavior
(2009) Divya Gautam; Rishi Raj Singh; Vivek Kumar Singh
A deeper understanding of emergence of global patterns in social systems such as diffusion of ideas, emergence of norms & conventions, higher organizations, collective wisdom and evolution of culture; through simple and predictable local interactions of individuals, has been a long quest for sociologists. Agent-based modeling is the latest approach which has virtually replaced the use of traditional techniques of equation based models & micro simulations for social systems analysis. This new paradigm, in addition to being applied to model & analyze various social systems, is also finding widespread application in diverse domains such as economics, business organizations and computational systems. The findings of agent-based models of social systems not only help obtaining a better understanding of the investigated phenomenon but also provide valuable inputs for design of agent-based computational formulations for solving different problems in varied domains. In this paper, we have tried to characterize the use of multi-agent based modeling approach of social contagion and emergent collective behavior along with our experimental work on neighbourhood aggregation model. The paper concludes with a short discussion of the relevant implications for multi-agent systems design. ©2009 IEEE.
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