Bioactive natural and semisynthetic latrunculins.
Marine-derived macrolides latrunculins A and B, of the Red Sea sponge Negombata magnifica, are the first marine natural products that have been found to reversibly bind to actin monomers and to disrupt its organization. Latrunculins are structurally related to many antimicrobial and antiangiogenic macrolides. Several grams of latrunculin B (1), together with a new latrunculin named latrunculin T (2), were isolated from a recent collection of N. magnifica. Semisynthetic modifications of 1, including acetylation, acetalization, and N-hydroxymethylation, afforded four new (4, 5, 7, 8) and two known (6 and 9) semisynthetic analogues. Specifically, 15-O-methyllatrunculin B (6) showed a promising antiangiogenic activity in a chick chorioallantoic membrane assay and antimigratory activity in Boyden's chamber assay. Moreover, latrunculin B (1) and the new N-acetyllatrunculin B (4) displayed potent antimigratory activity in a wound-healing assay. Natural and semisynthetic latrunculins showed potent antimicrobial activity against Candida albicans, Saccharomyces cerevisiae, Staphylococcus aureus, and Bacillus cereus. Latrunculins are potential leads that can be developed as anticancer and antimicrobial agents.
El Sayed
Khalid A
KA
Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Louisiana 71209, USA. elsayed@ulm.edu
Youssef
Diaa T A
DT
Marchetti
Dario
D
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001409:Bacillus cereus / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D019156:Indian Ocean; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D053778:Thiazolidines; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects*
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018942:Macrolides; D013844:Thiazoles; D053778:Thiazolidines; C037068:latrunculin B