THE ROLE OF CHIRALITY IN DRUG DESIGN AND DEVELOPMENT

The chirality, which plays an important role in pharmaceutical chemistry, which is non-superimposable mirror image of a molecule (enantiomers). Enzymes and receptors are chiral biological systems that hence, drug enantiomers tend to have different pharmacological and toxicological characteristics. The problem of chirality in clinical significance was brought to the forefront because of the Tragedy of thalidomide which led to significant changes in drug regulations and development. Stereoselective synthesis, chiral resolution and analytical technology have facilitated the synthesis of more effective and safer, enantiomerically pure drugs. Chirality affects the pharmacodynamics and pharmacokinetics where enantiomers can vary in terms of absorption, metabolism, receptor binding, and toxicity. The regulatory authorities (FDA and EMA) have also introduced the need to study enantiomers and with this, single enantiomer drugs (esomeprazole, levofloxacin, and levalbuterol) are emerging. Enantioselective drug discovery has also been further advanced by progress in asymmetric catalysis, biocatalysis, high-throughput screening, and computational modeling. Machine learning and artificial intelligence improve the prediction of enantiomer-target interactions, whereas the combination with the personalized medicine approach overcomes genetic and metabolic variability. Green and sustainable synthesis is being incorporated, making it cost effective and accessible. Altogether, chirality has been one of the pillars of contemporary drug design with the goal to create safer, more effective, and patient-specific therapies.