Chiral drugs: The future of precision medicine
image: Structures of L-lactate (1) and D-lactate (2)
Credit: Shou-jiao Peng, Yu-ying Zhu, Chun-ying Luo, Pei Zhang, Fei-yun Wang, Rui-xiang Li, Guo-qiang Lin, Jian-ge Zhang.
Key Points:
1. Chirality in Drug Development
Chiral drugs contain non-superimposable mirror-image forms (enantiomers) that can exhibit drastically different pharmacological effects.
Over 60% of current drugs are chiral, highlighting their importance in medicine.
2. Sources of Chiral Drugs
Natural extraction: Derived from plants (e.g., artemisinin, taxol).
Chemical synthesis: Asymmetric synthesis and chiral auxiliaries enable precise enantiomer production.
Biocatalysis: Enzymes offer green, efficient routes to single-enantiomer drugs (e.g., simvastatin).
3. Pharmacological Differences
- Same activity: Rare cases (e.g., fluoxetine).
- Quantitative differences: One enantiomer is active (e.g., S-ibuprofen), while the other is inactive.
- Qualitative differences: Enantiomers may have opposing effects (e.g., R-thalidomide is therapeutic; S-thalidomide is toxic).
4. Traditional Chinese Medicine (TCM) Contributions
Artemisinin: Nobel-winning antimalarial derived from TCM.
Triptolide: Potent anti-inflammatory/anticancer agent with ongoing structural optimization.
Panax notoginseng saponins (PNS): Cardiovascular protectors with multiple chiral saponins.
5. Future Directions
Scaling chiral separation and synthesis for complex TCM compounds.
Developing enantioselective biocatalysts and asymmetric synthesis methods.
Expanding chiral drug applications in precision medicine.
Conclusion:
Chiral drugs leverage the "handedness" of molecules to enhance drug efficacy and safety. Advances in synthesis, analysis, and TCM-derived chiral compounds are driving a new era of targeted therapies, with lessons from past failures (e.g., thalidomide) guiding future innovation.