Macrolides antifungal activity

A series of macrolides bearing a thiazole moiety have been isolated from tunicates and sponges. The tunicate Lissoclinum patella has afforded the patellazoles A-C (428-430), which were found to be potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3—10-6 pg/ml as well as exhibiting antifungal activity [334, 335]. Furthermore, patellazole B (429) exhibited very potent antiviral activity against Herpes symplex viruses [334],... 

The compounds isolated from the nudibranch Hexabranchus sanguineus varied with collecting location but usually included dihydrohalichondra-mide (261) and tetrahydrohalichondramide (268). Compounds 261, 263, 265, and 268 show antifungal activity and inhibit cell division in the fertilized sea urchin egg assay (218). Three cytotoxic macrolides, mycalolides A-C (269-271), were isolated from a Japanese sponge of the genus My-cale, and their structures were elucidated to be hybrids of ulapualides and halichondramide (219). 

The disorazole is comprised of a family of 29 closely related macrolides, which were isolated from the myxobacterium Soranghmi cellulosium. Disorazole Al, the major component of the crude extraction residue, possesses antifungal activity, decay of microtubules in subnanomolar concentration, initiates cell cycle arrest in G2/M phase, and competes in vitro with vinsblastine for the tublin binding site. The retrosynthetic disconnections of disorazole Al and a few stereoselective synthetic routes are described [12]. 

Most polyene macrolides show antifungal activity, and they are produced by actinomycetes. Polyene macrolides are precisely described in Chapters 9 and 12 of the first edition of this book [1]. Though a few octaene macrolides have been reported, their structures have not been elucidated. 

Patellazoles A-C (77-79), 24-membered thiazole-containing macrolides, were isolated from two specimens of didemnid tunicate, Lissoclinum patella, which were collected from the Fiji Islands [148] and Piti Bomb Holdes, Guam [149]. The patellazoles were potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10" to 10 pg/ml and antifungal activity against Candida albicans. 

Galbonolides. Macrolide antibiotics produced by Mi-cromonospora chalcea and Streptomyces galbus. G. A and G. B are structurally related to rustmicin. Both show antifungal activity, e.g., G. A C21H32O6, Mr 380.48, needles, mp. 68 °C, [alp-231° (acetone). 

C44H60N4O12, Mr 836.97, mp. 66-68 °C, [a]c -101° (CH3OH). A macrolide antibiotic with antifungal activity from Halichondria sponges. The structure is similar to those of ulapualides. 

Mr 999.17, oil). The compounds have antimicrobial and cytotoxic activity against L1210 cells (EDjq 0.01-0.03 pg/mL). A similar macrolide, kabiramide C (C48H,N50,4, Mr 942.12, amorphous, [a]o +20°), with antifungal activity is isolated from the egg mass of the nudibranch Dendrodoris nigra. ... 

Although they share structural features with the antibacterial macrolides and the antifungal macrocylic polyenes, the avermectins are not usually grouped with those compounds since they have neither antibacterial nor antifungal activities nor do they inhibit protein or chitin syntheses as do the other two groups. In the avermectins the macrocycle is a backbone for further substitution with a spiroketal (C-17 to C-28), a hexahydrobenzofuran unit (C-2 to C-8a), and... 

Cybulska B, Mazeiski J, Borowski E, Gaty-Bobo CM. Haemolytic activity of aromatic heptaenes. A group of polyene macrolide antifungal antibiotics. Biochem Pharmacol 1984 1 4 M6. 

Polyenes. These antifimgal macrolides differ from antibacterial macrolides in the size of the lactone ring, ranging from 26 to 38 atoms, and with the presence of a series of conjugated double bonds. The only member systemically used is amphotericin B, produced by Streptomyces nodosus. Antifungal activity is due to interference with membrane sterols, resulting in permeability alteration (O Fig. 9.5). 

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