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Fundamental physical and chemical concepts behind “drug-likeness” and “natural product-likeness”

Mohd AtharORCID iD: https://orcid.org/0000-0001-6337-1026 / Alfred Ndeme Sona / Boris Davy Bekono
  • Department of Physics, Ecole Normale Supérieure, University of Yaoundé I, P.O. Box 47, Yaoundé, Cameroon
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/ Fidele Ntie-Kang
  • Department of Chemistry, University of Buea, P. O. Box 63 Buea, Buea, Cameroon
  • Department of Pharmaceutical Chemistry, Martin-Luther University Halle-Wittenberg, Wolfgang-Langenbeck Str. 4, 06120 Halle (Saale), Germany
  • Department of Informatics and Chemistry, University of Chemistry and Technology Prague, Technická 5 166 28 Prague 6, Dejvice, Czech Republic
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Published Online: 2019-09-04 | DOI: https://doi.org/10.1515/psr-2018-0101


The discovery of a drug is known to be quite cumbersome, both in terms of the microscopic fundamental research behind it and the industrial scale manufacturing process. A major concern in drug discovery is the acceleration of the process and cost reduction. The fact that clinical trials cannot be accelerated, therefore, emphasizes the need to accelerate the strategies for identifying lead compounds at an early stage. We, herein, focus on the definition of what would be regarded as a “drug-like” molecule and a “lead-like” one. In particular, “drug-likeness” is referred to as resemblance to existing drugs, whereas “lead-likeness” is characterized by the similarity with structural and physicochemical properties of a “lead”compound, i.e. a reference compound or a starting point for further drug development. It is now well known that a huge proportion of the drug discovery is inspired or derived from natural products (NPs), which have larger complexity as well as size when compared with synthetic compounds. Therefore, similar definitions of “drug-likeness” and “lead-likeness” cannot be applied for the NP-likeness. Rather, there is the dire need to define and explain NP-likeness in regard to chemical structure. An attempt has been made here to give an overview of the general concepts associated with NP discovery, and to provide the foundational basis for defining a molecule as a “drug”, a “lead” or a “natural compound.”

Keywords: fragment analysis; drug discovery; natural products; natural product score


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Published Online: 2019-09-04

Citation Information: Physical Sciences Reviews, 20180101, ISSN (Online) 2365-659X, DOI: https://doi.org/10.1515/psr-2018-0101.

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