Substituted adamantylphthalimides: Synthesis, antiviral and antiproliferative activity.

Abstract

In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4'-R2 )phthalimidoadamantanes (1-7), 3-[N-(4'-R2 )phthalimido]-1-adamantanols (8-10), and 3-[N-(4'-R2 )phthalimido]adamantane-1-carboxylic acids (11-15), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH2 substituent at the phthalimide (compounds 3 and 5). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5, but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities.

• Authors: Leo Mandić, Patricia Benčić, Kata Mlinarić-Majerski, Sandra Liekens, Robert Snoeck, Graciela Andrei, Marijeta Kralj, Nikola Basarić
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 353 Issue 6 Pg. e2000024 (Jun 2020) ISSN: 1521-4184 [Electronic] Germany
• PMID: 32285536 (Publication Type: Journal Article)
• Copyright: © 2020 Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Phthalimides
• phthalimide
• Adamantane

Topics

• Adamantane (analogs & derivatives, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line
• Cell Proliferation (drug effects)
• Cytomegalovirus (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Herpesvirus 3, Human (drug effects)
• Humans
• Microbial Sensitivity Tests
• Molecular Structure
• Phthalimides (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship