To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability

Authors

  • Mariana Celestina Frojuello Costa Bernstorff Damião Faculty of Pharmaceutical Sciences University of São Paulo, Brazil
  • Kerly Fernanda Mesquita Pasqualoto Biochemistry and Biophysics Laboratory, Butantan Institute, Brazil
  • Michelle Carneiro Polli Department of Pharmacy, São Francisco University, Brazil
  • Roberto Parise Filho Faculty of Pharmaceutical Sciences University of São Paulo, Brazil

DOI:

https://doi.org/10.18433/J3BS4H

Abstract

Purpose. Prodrug design is a strategy that can be used to adjust physicochemical properties of drugs in order to overcome pharmacokinetic problems, such as poor oral bioavailability. However, Lipinski´s and Veber´s rules predict whether compounds will have absorption problems even before the design of prodrugs. In this context, our goal was to evaluate the molecular properties which most influenced the absorption process of prodrugs compared to its precursor through exploratory data analysis approach.  Methods: A variety of prodrugs and respective precursors were randomly selected and classified by its percentage of human intestinal absorption. Subsequently, different molecular properties were calculated and hierarchical cluster analysis (HCA) and principal components analysis (PCA) were carried out.  Results: According to the findings, antiviral, anti-hypertensive, and antibiotic prodrugs exhibited higher absorption levels than their respective precursors. Also, some relevant descriptors (molecular weight, MW, routable bonds, rot_bonds, hydrogen bond acceptors, HBA_count and polar surface area, PSA), which are included in Lipinski´s and Veber´s rules, influenced the separation process between prodrugs and drugs. Furthermore, other molecular properties, such as polarizability (α) and molar refractivity (MR), were pointed out. Conclusion: Lipinski´s and Veber´s rules proved to be important to design an orally administered drug but other descriptors should be considered by medicinal chemists in the prodrug designing process.

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Author Biography

Roberto Parise Filho, Faculty of Pharmaceutical Sciences University of São Paulo, Brazil

Department of Pharmacy

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Published

2014-11-06

How to Cite

Damião, M. C. F. C. B., Pasqualoto, K. F. M., Polli, M. C., & Parise Filho, R. (2014). To Be Drug or Prodrug: Structure-Property Exploratory Approach Regarding Oral Bioavailability. Journal of Pharmacy & Pharmaceutical Sciences, 17(4), 532–540. https://doi.org/10.18433/J3BS4H

Issue

Section

Pharmaceutical Sciences; Original Research Articles