Exploring Privileged Structure Repurposing: Target Similarity as a Catalyst for Cross-Species Drug Discovery.

7-azaindole as privileged scaffold: Advances in drug design and structural modification

Emerging biochemical and bioanalytical strategies shaping nature-based therapeutic discovery.

It is proposed that systematic integration of NP-inspired scaffolds with modern discovery platforms and computational tools, represents the most productive current framework for targeting disease-relevant complexes previously considered inaccessible, expanding the boundary of druggability across oncology, cardiovascular, and metabolic medicine.

The Pyrazolone Scaffold: A Privileged Motif for Molecular Hybridization in Drug Discovery.

Pyrazolone and its keto-enol tautomers constitute a privileged class of scaffolds in contemporary medicinal chemistry, characterized by remarkable structural plasticity. This review comprehensively summarizes recent advancements in the structural optimization of pyrazolone-based compounds, highlighting how molecular hybridization drives polypharmacology against complex conditions, including neurodegenerative disorders, inflammation, metabolic syndromes, cancer, and infectious diseases. By detailing structure-activity relationships, the review elucidates how the strategic pharmacophore merging at the N-1, C-3, and C-4 positions transforms the pyrazolone core into highly potent therapeutics. Mechanistically, these hybrid molecules exhibit diverse capabilities, such as inhibiting key survival kinases, blocking pathogenic protein aggregation, antagonizing immune checkpoints, and restoring cellular redox homeostasis via robust reactive oxygen species scavenging. Ultimately, this review underscores the critical role of molecular hybridization in overcoming drug resistance, minimizing systemic toxicity, and driving the future discovery of pyrazolone-based precision therapeutics.

Adventures in Chemical Space: From Targets to Drugs to Design Principles.

The central theme, conformational analysis, links on-target potency via pre-organization of the bioactive conformation with physics-based physicochemical property prediction with physics-based physicochemical property prediction, highlighting neutral polarity as a key determinant of permeability and exposure.

Molecular docking approaches in drug repurposing: A mini review

Drug repurposing has emerged as an effective strategy to accelerate the drug discovery process by identifying new therapeutic applications for existing drugs. Among the various computational techniques employed in drug repurposing, molecular docking has gained significant importance due to its ability to predict ligand–protein interactions, binding affinity, and molecular stability with high efficiency and reduced cost. The present mini review highlights the fundamental principles, methodologies, and applications of molecular docking in drug repurposing research. Different docking approaches, including rigid docking, flexible docking, and induced-fit docking, along with commonly used software such as AutoDock, Glide, GOLD, and Schrödinger Suite, are discussed. The review further emphasizes the wide applications of molecular docking in identifying potential therapeutics for infectious diseases, cancer, neurodegenerative disorders, and cardiovascular diseases. Particular attention is given to the role of docking studies during the COVID-19 pandemic, where several approved drugs were rapidly screened against SARS-CoV-2 targets. In addition, recent advances involving artificial intelligence, machine learning, molecular dynamics simulations, network pharmacology, and structural bioinformatics have considerably improved the accuracy and efficiency of docking-based drug repurposing studies. Despite these advancements, challenges such as protein flexibility, inaccuracies in scoring functions, computational limitations, and false-positive predictions remain major concerns. Therefore, integration of docking with complementary computational and experimental approaches is essential for improving prediction reliability and therapeutic validation. Overall, molecular docking continues to serve as a powerful and economical tool in modern drug repurposing research, offering promising opportunities for accelerated drug discovery and precision medicine.

Unlocking the pharmacological potential of rhodanine derivatives: Drug design strategies and structure-activity relationships

Abstract The rhodanine core or 2-thioxothiazolidin-4-one, a five-membered heterocyclic ring system, has garnered significant interest in drug discovery, owing to its diverse biological activities. Derivatization of rhodamine has yielded many clinically useful therapeutic compounds for various ailments due to the presence of both nitrogen and sulfur heteroatoms within its ring system. Its broad-spectrum activities are facilitated by its two key electrophilic binding groups, ketone and thioketone, which enable interactions with various biological targets. Significant advances have been made toward its efficient synthetic strategies for drug discovery and development. This comprehensive review discusses rational design strategies for rhodanine-based heterocycles and their therapeutic potential as antibacterial, anti-diabetes, anti-Alzheimer’s, anticancer, anthelmintic, anti-obesity, and against COVID-19. The article also sheds light on the synthetic strategies used to develop rhodamine derivatives and drug design supported with detailed structure-activity relationships (SAR). Further molecular docking providing mechanistic insights into their binding modes within receptors are also presented. These structural insights could help in further rational design of potent rhodamine derivatives as newer and safer therapeutic agents. Graphical AbstractCentral yellow molecular structure linked to various disease icons: anticancer, antibacterial, anti-Alzheimer, anti-COVID-19, antidiabetic, and anthelmintic.The diagram presents a central yellow molecular structure with elements like nitrogen (N), sulfur (S), and oxygen (O). It illustrates connections to diverse biological applications: anticancer, antibacterial, anti-Alzheimer, anti-COVID-19, antidiabetic & anti-obesity, and anthelmintic, represented by icons in surrounding circles. A curved green line labeled "Structure Activity Relationship" encircles the categories. Above, a labeled 'Drug Design' oval and precursor molecules R-NH2, ClCH2COOH, and CS2 are included, visually connecting the drug synthesis process and biological targets.