{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:50:46Z","timestamp":1784094646105,"version":"3.55.0"},"reference-count":0,"publisher":"Frontiers Media SA","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharm Pharm Sci"],"abstract":"<jats:p>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\u00b4s and Veber\u00b4s 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.\u00a0 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.\u00a0 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\u00b4s and Veber\u00b4s rules, influenced the separation process between prodrugs and drugs. Furthermore, other molecular properties, such as polarizability (\u03b1) and molar refractivity (MR), were pointed out. Conclusion: Lipinski\u00b4s and Veber\u00b4s 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.<\/jats:p>","DOI":"10.18433\/j3bs4h","type":"journal-article","created":{"date-parts":[[2016,9,2]],"date-time":"2016-09-02T00:33:15Z","timestamp":1472776395000},"page":"532","source":"Crossref","is-referenced-by-count":16,"title":["To Be Drug or Prodrug:  Structure-Property Exploratory Approach Regarding Oral Bioavailability"],"prefix":"10.3389","volume":"17","author":[{"given":"Mariana Celestina Frojuello Costa Bernstorff","family":"Dami\u00e3o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerly Fernanda Mesquita","family":"Pasqualoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle Carneiro","family":"Polli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Parise Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2014,11,6]]},"container-title":["Journal of Pharmacy &amp; Pharmaceutical Sciences"],"original-title":[],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T13:34:36Z","timestamp":1673616876000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.library.ualberta.ca\/jpps\/index.php\/JPPS\/article\/view\/23063"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,6]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,10,4]]}},"URL":"https:\/\/doi.org\/10.18433\/j3bs4h","relation":{},"ISSN":["1482-1826","1482-1826"],"issn-type":[{"value":"1482-1826","type":"electronic"},{"value":"1482-1826","type":"print"}],"subject":[],"published":{"date-parts":[[2014,11,6]]}}}