Synthesis, antimicrobial and antineoplastic activities for agelasine and agelasimine analogs with a beta-cyclocitral derived substituent.
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.
Proszenyák
Agnes
A
Department of Chemistry, University of Oslo, Oslo, Norway.
Charnock
Colin
C
Hedner
Erik
E
Larsson
Rolf
R
Bohlin
Lars
L
Gundersen
Lise-Lotte
LL
D000048:Acanthamoeba / Q000187:drug effects; D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D047230:Agelas / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009284:Naphthols / Q000737:chemistry; D011687:Purines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000447:Aldehydes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000977:Antiparasitic Agents; D004224:Diterpenes; D006146:Guanidines; D009284:Naphthols; D011687:Purines; D013729:Terpenes; C509934:agelasine D; C412407:agelasine F; C060682:agelasimine A; C060683:agelasimine B; C516118:beta-cyclocitral; D000225:Adenine