Biology subjects

Regati, D. R.

Publications and source records attributed to Regati, D. R..

3 recordsLinked to original sources

bioRxiv2025

GRAYU: Graph-based Database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases

The translation of Indias extensive traditional knowledge on indigenous medicinal plants into modern therapeutic solutions is contingent upon a systematic framework. While traditional Indian medicine offers a rich source of therapeutic leads, this knowledge is often not structured for modern computational analysis, creating a barrier to systematic drug discovery. To this end, we present GRAYU, a curated and comprehensive online database that integrates data across multiple categories, connecting 1039 traditional formulations to 12,949 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases. It also provides insights into 1,382,362 plant-phytochemical, 116,824 plant-disease, 2,405 plant-formulation, and 4,087 formulation-disease associations. Case studies on phytochemical analogs, sustainable plant substitution, and disease-network pharmacology showcased the potential of integrative graphs to decode shared molecular signatures and therapeutic networks across traditional Ayurvedic formulations. GRAYU represents a user-friendly resource for researchers to investigate complex bio-associations and formulate novel therapeutic hypotheses, with insights from traditional Indian medicine. GRAYU is available at https://caps.ncbs.res.in/GRAYU/.

bioinformatics↗

bioRxiv2025

Rational design and comparative docking and simulation of modified FLT3 inhibitors: A study on enhanced binding stability and inhibition potency

The FLT3 protein is a well-established therapeutic target in the treatment of Acute Myeloid Leukemia (AML), with its inhibition playing a crucial role in disease management. In this study, we identify and propose a novel FLT3 inhibitor that demonstrates superior binding affinity, stability, and pharmacokinetic properties compared to currently available inhibitors. We initially characterized the binding interactions of known FLT3 inhibitors through molecular docking and then strategically modified functional groups to enhance binding affinity, optimize drug-likeness, and minimize toxicity. The resulting analogue exhibits improved metabolic stability, lower toxicity, higher intestinal absorption, and superior permeability. Molecular dynamics simulations further confirm that the novel inhibitor forms stable and persistent interactions with FLT3, as evidenced by reduced conformational fluctuations and compact structural integrity. Free energy calculations reveal stronger ligand stabilization, while dynamic correlation analysis suggests enhanced engagement with critical residues, reinforcing its potential as an effective therapeutic agent. These findings highlight a promising candidate for further experimental validation and potential development in AML treatment.

cancer biology↗

bioRxiv2024

Exploration of Natural Products for Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia Through Ligand-Based Pharmacophore Screening and Molecular Dynamic Simulation Approaches

BackgroundMutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are prevalent drivers of acute myeloid leukemia (AML). While targeted therapies exist, resistance can emerge. This study explored the potential of natural products to identify novel dual IDH inhibitors. MethodsIn-silico screening of the COCONUT database was performed using Lipinskis Rule of Five. Pharmacophore modelling identified crucial features for IDH binding. Docking simulations with Glide (Schrodinger) assessed binding affinity, followed by MM-GBSA calculations for free energy estimation. The most promising candidate underwent ADME/T and toxicity analysis. Finally, molecular dynamics (MD) simulations evaluated the stability of protein-ligand complexes and binding interactions, followed by trajectory analysis using DCCM and PCA. ResultsThe study identified Ternstroside D (CNP0166496) as a potential dual inhibitor for IDH1 and IDH2 mutations. Docking simulations and MM-GBSA calculations predicted favourable binding affinities. MD simulations revealed stable protein-ligand complexes, and in-silico ADME/T analysis suggested good drug-like properties and a favorable safety profile for CNP0166496. ConclusionThis in-silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Further in-vitro and in-vivo studies are warranted to validate these findings.

bioinformatics↗