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Keywords = time-dependent chemoinformatic analysis

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20 pages, 7815 KB  
Article
Time-Dependent Comparison of the Structural Variations of Natural Products and Synthetic Compounds
by Yi Liu, Mingzhu Cai, Yuxin Zhao, Zilong Hu, Ping Wu and De-Xin Kong
Int. J. Mol. Sci. 2024, 25(21), 11475; https://doi.org/10.3390/ijms252111475 - 25 Oct 2024
Cited by 3 | Viewed by 2617
Abstract
The identification of natural products (NPs) has played a pivotal role in drug discovery and shaped the evolution of synthetic compounds (SCs). However, the extent to which NPs have historically influenced the structural characteristics of SCs remains unclear. In this study, we conducted [...] Read more.
The identification of natural products (NPs) has played a pivotal role in drug discovery and shaped the evolution of synthetic compounds (SCs). However, the extent to which NPs have historically influenced the structural characteristics of SCs remains unclear. In this study, we conducted a comprehensive, time-dependent chemoinformatic analysis to investigate the impact of NPs on the structural evolution of SCs. The physicochemical properties, molecular fragments, biological relevance, and chemical space of the molecules from the Dictionary of Natural Products were compared in a time series fashion with a synthetic compound collection sourced from 12 databases. Our findings reveal that NPs have become larger, more complex, and more hydrophobic over time, exhibiting increased structural diversity and uniqueness. Conversely, SCs exhibit a continuous shift in physicochemical properties, yet these changes are constrained within a defined range governed by drug-like constraints. SCs possess a broader range of synthetic pathways and structural diversity, albeit with a decline in biological relevance. The chemical space of NPs has become less concentrated compared to that of SCs. In conclusion, our study suggests that the structural evolution of SCs is influenced by NPs to some extent; however, SCs have not fully evolved in the direction of NPs. Full article
(This article belongs to the Special Issue Natural Products and Synthetic Compounds for Drug Development 2.0)
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