| 1. |
- Proszenyák, Agnes, et al.
(author)
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Synthesis, antimicrobial and antineoplastic activities for agelasine and agelasimine analogs with a beta-cyclocitral derived substituent.
- 2007
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In: Archiv der Pharmazie. - : Wiley. - 0365-6233 .- 1521-4184. ; 340:12, s. 625-634
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Journal article (peer-reviewed)abstract
- Agelasines and agelasimines are antimicrobial and cytotoxic purine derivatives isolated from marine sponges (Agelas sp.). We have synthesized structurally simplified analogs of these natural products starting from beta-cyclocitral. The novel compounds were found to be strong inhibitors of a wide variety of pathogenic microorganisms (incl. Mycobacterium tuberculosis) as well as cancer cell lines. The biological activities were generally in the same range as those previously found for the structurally more complex agelasines and agelasimines isolated in small amounts from natural sources. We also report for the first time that agelasine and agelasimine analogs inhibit growth of protozoa (Acanthamoeba castellanii and Acanthamoeba polyphaga). Acanthamoeba keratitis is an increasingly common and severe corneal infection, closely associated with contact lens wear.
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| 2. |
- Roggen, Heidi, et al.
(author)
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2-Substituted agelasine analogs : Synthesis and biological activity, and structure and reactivity of synthetic intermediates
- 2011
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In: Pure and Applied Chemistry. - 0033-4545 .- 1365-3075. ; 83:3, s. 645-653
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Journal article (peer-reviewed)abstract
- 2-Substituted N-methoxy-9-methyl-9H-purin-6-amines were synthesized either from their corresponding 6-chloro-9-methyl-9H-purines or 2-chloro-N-methoxy-9-methyl-9H-purin-6-amine. Great diversity in the amino/imino tautomeric ratios was observed and calculated based on H-1 NMR. The tautomers were identified by 1D and 2D H-1, C-13, and N-15 NMR techniques, and showed significant variation both in C-13 and N-15 shift values. Comparison of the tautomeric ratios with Hammett F values revealed that as the field/inductive withdrawing abilities of the 2-substituent increased, the ratio of amino: imino tautomers was shifted toward the amino tautomer. Computational chemistry exposed the significance of hydrogen bonding between solvent and the compound in question to reach accurate predictions for tautomeric ratios. B3LYP/def2-TZVP density functional theory (DFT) calculations resulted in quantitatively more accurate predictions than when employing the less expensive BP86 functional. N-7-Alkylation of the 2-substituted N-methoxy-9-methyl-9H-purin-6-amines showed that when the field/inductive withdrawing ability of the 2-substituent reached a certain point the reactivity drastically dropped. This correlated with the atomic charges on N-7 calculated using a natural bond orbital (NBO) analysis. Biological screening of the final 2-substituted agelasine analogs indicated that the introduction of a methyl group in the 2-position is advantageous for antimycobacterial and antiprotozoal activity, and that an amino function may improve activity against several cancer cell lines.
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| 3. |
- Roggen, Heidi, et al.
(author)
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Antimicrobial and antineoplastic activities of Agelasine analogs modified in the purine 2-position
- 2011
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In: Archiv der Pharmazie. - : Wiley. - 0365-6233 .- 1521-4184. ; 344:1, s. 50-55
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
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| 5. |
- Vik, Anders, et al.
(author)
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Antimicrobial and cytotoxic activity of agelasine and agelasimine analogs
- 2007
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:12, s. 4016-4037
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Journal article (peer-reviewed)abstract
- Agelasine and agelasimine derivatives with substantially less complicated terpenoid side chains compared to the naturally occurring compounds have been synthesized and their ability to inhibit growth of microorganisms and cancer cells has been studied. Compounds with excellent activity against cancer cell lines (MIC ca. 1 μM for the most potent compounds), including a drug resistant renal cell line, have been identified. Most compounds studied also exhibited broad spectrum antimicrobial activity including activity against Mycobacterium tuberculosis.
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