Physicochemical Properties of Conventional Antiparasitic Drugs Based on Lipinski’s Rule of Five
Keywords:
antiparasitic, leishmaniasis, Lipinski's rule, physicochemical properties, rule of five.Abstract
Introduction: Infections caused by protozoan parasites and helminths are responsible for significant morbidity and mortality in both tropical and subtropical regions. In the antiparasitic drug discovery process, a number of generic criteria have been identified, including physicochemical properties that might predict oral therapy. According to them, an ideal molecule would comply with Lipinski's rule of five (RO5).
Objective: In this work, a general analysis based on physicochemical properties was performed for antiparasitic drugs for clinical use against the main parasitic protozoa and helminths of medical importance.
Methods: The chemical structure of 57 antiparasitic compounds was drawn in the Biovia draw program and the physicochemical properties were automatically improved, allowing the results to be analyzed according to Lipinski's rule.
Results: The first analysis showed that of 57 antiparasitics, 80.7% (n = 46) complied with Lipinski's rule; while amphotericin B and suramin fail 3 rules. On the other hands, among the diseases, the most critical compounds that did not meet RO5 are those recommended against leishmaniosis, with three of the drugs included in conventional therapy. Finally, although most antiparasitics are administered orally, some of these compounds fail in one or two RO5 parameters; while compounds that should be administered parenterally fail up to 3 rules.
Conclusion: In this work, we can suggest that the development of antiparasitic drugs, those that demonstrated pharmacological potential should not lose priority if the physicochemical parameters are outside the desirable range, particularly against leishmaniasis.
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