Antimicrobial and Antineoplastic Activities of Agelasine Analogs Modified in the Purine 2-Position

• Published in: Archiv der Pharmazie (Weinheim) 2011-01, Vol.344 (1), p.50-55
• Main Authors: Roggen, Heidi, Charnock, Colin, Burman, Robert, Felth, Jenny, Larsson, Rolf, Bohlin, Lars, Gundersen, Lise-Lotte
• Format: Article
• Language: English
• Subjects: Agelas; Agelasine; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Anticancer acivitity; Antifungal activity; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiparasitic Agents - chemical synthesis; Antiparasitic Agents - chemistry; Antiparasitic Agents - pharmacology; Antiprotozoal activity; Candida albicans; Candida krusei; Cell Line; Cell Line, Tumor; Cercopithecus aethiops; Escherichia coli; FARMACI; Humans; Leishmania infantum; Marine; Medical research; Mycobacterium tuberculosis; Neoplasms - drug therapy; Neoplasms - pathology; PHARMACY; Plasmodium falciparum; Protozoa; Purines - chemical synthesis; Purines - chemistry; Purines - pharmacology; Staphylococcus aureus; Structure-Activity Relationship; Trypanosoma brucei; Trypanosoma cruzi; Vero Cells
• ISSN: 0365-6233; 1521-4184; 1521-4184
• DOI: 10.1002/ardp.201000148

Agelasines are 7,9‐dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2‐position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U‐937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC‐5 cells. The results indicate that the introduction of a methyl group in the purine 2‐position is beneficial for antimycobacterial and antiprotozoal activity, and that amino groups may enhance activity against several cancer cell lines. Agelasine analogs modified in the purine 2‐position have been synthesized and examined for biological activities against a variety of patogenic microorganisms as well as cancer cell lines. The introduction of a methyl group in the 2‐position appears to improve antimycobacterial activity as well as antiprotozoal activity against pathogens causing severe tropical diseases. A primary or secondary amino group in the purine 2‐position may enhance activity against several cancer cell lines.