(3E,5E,7S,8S,11E,13E,15S,16S)-8,16-bis[(2S,3R,4S)-4-[(2R,4R,5R,6R)-4-{[(2R,4S,5S,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-5-ethyl-2-hydroxy-6-methyloxan-2-yl]-3-hydroxypentan-2-yl]-7,15-dimethyl-1,9-dioxacyclohexadeca-3,5,11,13-tetraene-2,10-dione

• ChemBase ID: 72682
• Molecular Formular: C54H88O18
• Molecular Mass: 1025.26572
• Monoisotopic Mass: 1024.59706598
• SMILES: [C@H]1([C@@H]([C@@H](O[C@H](C1)O[C@H]1[C@H](CC)[C@H](O[C@](C1)([C@H]([C@@H]([C@@H]([C@H]1OC(=O)/C=C/C=C/[C@@H]([C@H](OC(=O)/C=C/C=C/[C@@H]1C)[C@H]([C@H]([C@@H]([C@]1(C[C@H]([C@@H]([C@H](O1)C)CC)O[C@H]1C[C@@H]([C@@H]([C@@H](O1)C)O)O)O)C)O)C)C)C)O)C)O)C)C)O)O
• Canonical SMILES: CC[C@H]1[C@H](O[C@H]2C[C@H](O)[C@@H]([C@@H](O2)C)O)C[C@](O[C@@H]1C)(O)[C@H]([C@@H]([C@@H]([C@H]1OC(=O)/C=C/C=C/[C@H](C)[C@H](OC(=O)/C=C/C=C/[C@@H]1C)[C@H]([C@H]([C@@H]([C@@]1(O)C[C@@H](O[C@H]2C[C@H](O)[C@@H]([C@@H](O2)C)O)[C@@H]([C@H](O1)C)CC)C)O)C)C)O)C
• InChI: InChI=1S/C54H88O18/c1-13-37-33(9)71-53(63,25-41(37)67-45-23-39(55)49(61)35(11)65-45)31(7)47(59)29(5)51-27(3)19-15-17-22-44(58)70-52(28(4)20-16-18-21-43(57)69-51)30(6)48(60)32(8)54(64)26-42(38(14-2)34(10)72-54)68-46-24-40(56)50(62)36(12)66-46/h15-22,27-42,45-52,55-56,59-64H,13-14,23-26H2,1-12H3/b19-15+,20-16+,21-18+,22-17+/t27-,28-,29-,30-,31-,32-,33+,34+,35-,36-,37+,38+,39-,40-,41+,42+,45-,46-,47+,48+,49+,50+,51-,52-,53+,54+/m0/s1
• InChIKey: OSERMIPXNLXAPD-MJMYBOKFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3E,5E,7S,8S,11E,13E,15S,16S)-8,16-bis[(2S,3R,4S)-4-[(2R,4R,5R,6R)-4-{[(2R,4S,5S,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-5-ethyl-2-hydroxy-6-methyloxan-2-yl]-3-hydroxypentan-2-yl]-7,15-dimethyl-1,9-dioxacyclohexadeca-3,5,11,13-tetraene-2,10-dione
• IUPAC Traditional name: (3E,5E,7S,8S,11E,13E,15S,16S)-8,16-bis[(2S,3R,4S)-4-[(2R,4R,5R,6R)-4-{[(2R,4S,5S,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-5-ethyl-2-hydroxy-6-methyloxan-2-yl]-3-hydroxypentan-2-yl]-7,15-dimethyl-1,9-dioxacyclohexadeca-3,5,11,13-tetraene-2,10-dione
• Synonyms: Elaiophylin; Salbomycin; Gopalamicin; SNA 4606-3; Azalomycin-B

Database IDs

• CAS Number: 37318-06-2
• PubChem SID: 162037603
• PubChem CID: 6444206

CALCULATED PROPERTIES

• Acid pKa: 11.373988
• H Acceptors: 16
• H Donor: 8
• LogD (pH = 5.5): 6.398651
• LogD (pH = 7.4): 6.398606
• Log P: 6.3986516
• Molar Refractivity: 266.1378 cm^3
• Polarizability: 106.37813 Å^3
• Polar Surface Area: 269.82 Å^2
• Rotatable Bonds: 14
• Lipinski's Rule of Five: false

PROPERTIES

Physical Property

• Solubility: DMSO

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S1448

Research Area

• Description: Infection

Biological Activity

• Description: Azalomycin-B (Elaiophylin) shows antiprotozoal activity against Plasmodium falciparum K1a and Trypanosoma brucei brucei GUTat 3.1 strains with IC50 of 0.36 μM and 0.45 μM, respectively.
• In Vitro: Azalomycin-B possesses an antibacterial activity against Gram-positive bacteria. The minimum inhibitory concentration (MIC) of Azalomycin-B against Staphylococcus aureus (SG 511, 285 and 503) is 1.52 μM. The MIC of Azalomycin-B against Streptococcus pyogenes is 0.76 μM and 1.52 μM for strains 306A, and 77A, respectively. The MIC of Azalomycin-B against S. faecium A is 3.05 μM. ^[1] In vitro, Azalomycin-B shows an antibiotic activity as a rumen fermentation efficiency enhancer and also inhibits lactic acid production in the rumen fluid with IC5O of 2.14 μM. ^[2] Azalomycin-B inhibits P-type ATPases such as the P-type, K^+-dependent ATPase from Escherichia coli, without affecting F-type and V-type ATPases at all. ^[3] Azalomycin-B shows the potent cytotoxic effect on L929 mouse fibroblast cells, K562 human leukemia cells and HeLa cell cultures with IC50 of 0.29 μM, 0.19 μM and 0.29 μg/mL, respectively. ^[4] Moreover, Azalomycin-B also produces the cytotoxicity in MRC-5 cells with IC50 of 0.85 μM. ^[5]
• Features: Azalomycin-B is a macrolide antibiotic showing the antiprotozoal activity against Plasmodium falciparum K1a and Trypanosoma brucei brucei GUTat 3.1 strains.

Combination Therapy

• Description: Azalomycin-B (μg/mL) markedly enhances Rapamycin (μg/mL)'s antifungal activity against Candida albicans ATCC 11651 as high as 219%. ^[6]

Protocol

• Protocol: Cell Assay ^[4]
• Cell Lines: L92, K562 and HeLa cells
• Concentrations: 0-10 μM
• Incubation Time: 72 hours
• Methods: The adherent mouse fibroblast cell line L-929 is cultured in Eagle's MEM with 0.35 mg/mL sodium bicarbonate, 100 units/mL penicillin/100 μg/mL streptomycin, 10 mM HEPES, and 10% heat-inactivated FBS at 37 °C in culture flasks. The adherent cells are harvested at the logarithmic growth phase after trypsination using 0.05% trypsin in phosphate-buffered saline (PBS) containing 0.02% EDTA. The nonadherent human leukemia cell line K-562, is cultured in RPMI 1640 medium, supplemented with 100 units/mL penicillin/100 μg/mL streptomycin and 10% FBS in culture flasks. L-929 and K-562 cells are inoculated in 0.1 mL culture medium, containing NaHCO₃ without HEPES, per well of the 96-well microplates. The plates are previously prepared with dilutions of the Azalomycin-B in 0.1 mL medium. The microplates are kept for 72 hour at 37 °C in a humidified atmosphere containing 5% CO₂. The adherent human cell line HeLa is cultured in MEM Eagle with 100 units/mL penicillin/100 μg/mL streptomycin, 10% FBS, and 2 mM l-glutamine in vented culture flasks. The adherent cells are harvested during the logarithmic growth phase after trypsination with 0.4% trypsin in PBS containing 0.02% EDTA. These cells are seeded with in 0.1 mL culture medium per well of the 96-well microplates. HeLa cells are preincubated 48 hours without Azalomycin-B. The dilutions of Azalomycin-B are carried out on the monolayer of HeLa cells after preincubation time. After incubation, the monolayer of the adherent L-929 and HeLa cells are fixed by glutaraldehyde and stained with a 0.05% solution of methylene blue for 15 minutes. After washing the stain is eluted by 0.2 mL of 0.33 N HCl in the wells. The optical densities are measured at 630 nm in a Dynatech MR 7000 microplate reader. After incubation, the K-562 cells are analyzed using an electronic cell analyzer system CASY 1 and software CASYSTAT for determination of IC50 values. The IC50 values are determined by integrated software CASYSTAT.

References

• References: [1] Hammann P, et al. J Antibiot (Tokyo). 1990, 43(11), 1431-1440.
• References: [2] Liu CM, et al. J Antibiot (Tokyo). 1993, 46(2), 350-352.
• References: [3] Dröse S, et al. Biochemistry. 1993, 32(15), 3902-3906.
• References: [4] Ritzau M, et al. J Nat Prod. 1998, 61(11), 1337-1339.
• References: [5] Otoguro K, et al. J Antibiot (Tokyo). 2010, 63(5), 275-277.
• References: [6] Fang A, et al. J Antibiot (Tokyo). 2000, 53(2), 158-162.

REFERENCES

• Hammann P, et al. J Antibiot (Tokyo). 1990, 43(11), 1431-1440.
• Liu CM, et al. J Antibiot (Tokyo). 1993, 46(2), 350-352.
• Dröse S, et al. Biochemistry. 1993, 32(15), 3902-3906.
• Ritzau M, et al. J Nat Prod. 1998, 61(11), 1337-1339.
• Otoguro K, et al. J Antibiot (Tokyo). 2010, 63(5), 275-277.
• Fang A, et al. J Antibiot (Tokyo). 2000, 53(2), 158-162.