2. Academic Validation
  3. Drug discovery and optimization based on the co-crystal structure of natural product with target

Drug discovery and optimization based on the co-crystal structure of natural product with target

  • Eur J Med Chem. 2024 Feb 15:266:116126. doi: 10.1016/j.ejmech.2024.116126.
Xing Chen 1,  Swapna Varghese 2,  Zhaoyan Zhang 3,  Juncheng Du 4,  Banfeng Ruan 5,  Jonathan B Baell 6,  Xinhua Liu 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, PR China; School of Public Health, Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, 230032, PR China. Electronic address: [email protected].
  • 2 Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia. Electronic address: [email protected].
  • 3 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, PR China. Electronic address: [email protected].
  • 4 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, PR China. Electronic address: [email protected].
  • 5 Key Lab of Biofabrication of Anhui Higher Education, Hefei University, Hefei, 230601, PR China. Electronic address: [email protected].
  • 6 Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria, 3052, Australia. Electronic address: [email protected].
  • 7 School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, PR China. Electronic address: [email protected].
PMID: 38232464 DOI: 10.1016/j.ejmech.2024.116126
Abstract

Due to their structural diversities and prevalent biological activities, natural products (NPs) are momentous resources for drug discovery. Although NPs have a wide range of biological activities, many exhibit structural complexity that leads to synthetic difficulties, which combines with inefficient biological activity, toxicity, and unfavorable pharmacokinetic characteristics and ultimately imparts poor safety and efficacy outcomes. Progress in crystallization and computational techniques allow crystallography to have a seasonable influences on drug discovery. By co-crystallizing with proteins, therapeutic targets of NPs in specific diseases can be identified. By analyzing the co-crystal information, the structure-activity relationships (SARs) of NPs targeting specific proteins can be grasped. Under the guidance of co-crystal information, directional structural modification and simplification are powerful strategies for overcoming limitations of NPs, improving the success rate of NP-based drug discovery, and obtaining NP-based drugs with high selectivity, low toxicity and favorable pharmacokinetic characteristics. Here, we review the co-crystal information of a selection of NPs, focusing on the SARs of NPs reflected by co-crystal information and the modification and simplification strategies of NPs, and discuss how to apply co-crystal information in the optimization of NP-based lead compound.

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