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.