53003-10-4

Usage

Uses

Used in Veterinary Medicine:
Salinomycin is used as an antibacterial agent for controlling coccidia in animals, which are parasitic protozoa that cause coccidiosis, a disease affecting the intestinal tract. Its anti-coccidial activity helps in preventing and treating this condition in livestock.
Used in Animal Husbandry:
In the animal husbandry industry, Salinomycin is utilized for growth promotion in ruminants, such as cattle and sheep. Its use contributes to improved weight gain and overall health of these animals.
Used in Cancer Research:
Salinomycin has been shown to inhibit cancer stem cells, demonstrating a potency greater than that of taxol by more than 100 times. Although the exact mechanism of action is not yet fully understood, its potential in cancer treatment is being explored, particularly in targeting CD44+CD24mesenchymal-like subpopulations within breast carcinomas.
Used in Analytical Chemistry:
Salinomycin is employed as a standard in the development of LC-MS/MS methods for the detection of residual coccidiostats in egg and muscle samples. This application aids in ensuring the safety and quality of these food products by monitoring the presence of these substances.

Biological Activity

salinomycin (sal), which is a polyether ionophore antibiotic from streptomyces albus, has been proven to be able to kill different types of human cancer cells, most likely via interfering with abc drug transporters, the wnt/β-catenin signaling pathway, or other pathways.

Biochem/physiol Actions

Salinomycin produced by Streptomyces albus is a carboxylic polyether ionophore with antibiotic and anti-cancer properties. It induces cell death in some types of cancer cells such as breast, lung, gastric cancer, leukemia and osteosarcoma. Salinomycin inhibits multidrug resistance protein 1 and induces apoptosis by the generation of reactive oxygen species that cause DNA damage and inactivation of Stat3. Use of salinomycin as antibiotic results in lowered spermatozoa count and motility and decreased steroidogenesis in mice.

in vitro

several hepatocellular carcinoma (hcc) cell lines were treated with sal. results showed that sal inhibited proliferation and decreased pcna levels. cell cycle analysis showed that sal caused cell cycle arrest in different phases. sal induced apoptosis as characterized by an increase in the bax/bcl-2 ratio. compared to control, β-catenin expression was down-regulated by sal treatment significantly. the ca2+ concentration in hcc cells was examined by flow cytometry and it was found that higher ca2+ concentrations were observed in sal treatment groups [1].

in vivo

the in vivo anti-tumor effect of sal was verified using the hepatoma orthotopic tumor model and results showed that the liver tumor size in sal-treated groups decreased. immunohistochemistry and tunel staining also demonstrated that sal could in vivo inhibit proliferation and induced apoptosis [1].

IC 50

7.7, 13.7 and 10.4 μm for hepg2, smmc-7721 and bel-7402 cell line, respectively (after 24h treatment)

references

[1] wang f,he l,dai wq,xu yp,wu d,lin cl,wu sm,cheng p,zhang y,shen m,wang cf,lu j,zhou yq,xu xf,xu l,guo cy. salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. plos one.2012;7(12):e50638.

InChI:InChI=1/C42H70O11.Na/c1-11-29(38(46)47)31-15-14-23(4)36(50-31)27(8)34(44)26(7)35(45)30(12-2)37-24(5)22-25(6)41(51-37)19-16-32(43)42(53-41)21-20-39(10,52-42)33-17-18-40(48,13-3)28(9)49-33;/h16,19,23-34,36-37,43-44,48H,11-15,17-18,20-22H2,1-10H3,(H,46,47);/q;+1/p-1/t23-,24-,25+,26-,27-,28-,29+,30-,31+,32+,33+,34+,36+,37-,39-,40+,41?,42-;/m0./s1

Upstream product

• 126574-63-8 21-episalinomycin 
• 110653-56-0 (R)-2-[(2R,5S,6R)-6-((S)-2-Hydroxy-1-methyl-ethyl)-5-methyl-tetrahydro-pyran-2-yl]-butyric acid 
• 110653-60-6 (2R,4S,5S,6S,7R)-6-ethyl-5,7-isopropylidenedioxy-2,4-dimethylnonanal 
• 120269-74-1 (2R,3R,6S)-6-((2R,5R,6S)-5-Benzyloxy-5-ethyl-6-methyl-tetrahydro-pyran-2-yl)-2-(4-methoxy-benzyloxy)-heptane-1,3,6-triol 
• 110653-78-6 Acetic acid (2S,9S,10S,12R,15R)-2-((2R,5R,6S)-5-ethyl-5-hydroxy-6-methyl-tetrahydro-pyran-2-yl)-9-((R)-1-ethyl-2-oxo-butyl)-2,10,12-trimethyl-1,6,8-trioxa-dispiro[4.1.5.3]pentadec-13-en-15-yl ester 
• 110672-02-1 (3S,4R,7S,8R,9S)-3-benzyloxymethyl-8,10-isopropylidenedioxy-7,9-dimethyl-4-vinyldecan-4-ol 
• 108470-05-9 5-O-benzyl-2,4-dideoxy-3-O-formyl-2,4-di-C-methyl-L-lyxose 
• 115181-73-2 (2S,3R,4S)-3,5-isopropylidenedioxy-2,4-dimethylpentanol 
• 120269-89-8 (R)-4-[(2S,5S,7S,9S,10S,12R)-2-[(2R,5R,6S)-5-Ethyl-5-(4-methoxy-benzyloxy)-6-methyl-tetrahydro-pyran-2-yl]-15-(4-methoxy-benzyloxy)-2,10,12-trimethyl-1,6,8-trioxa-dispiro[4.1.5.3]pentadec-13-en-9-yl]-hexan-3-one 
• 113643-46-2 (R)-4-[(2S,5S,7S,9S,10S,12R)-2-((2R,5R,6S)-5-Benzyloxy-5-ethyl-6-methyl-tetrahydro-pyran-2-yl)-15-(4-methoxy-benzyloxy)-2,10,12-trimethyl-1,6,8-trioxa-dispiro[4.1.5.3]pentadec-13-en-9-yl]-hexan-3-one 
• 113643-46-2 (R)-4-[(2S,5R,7S,9S,10S,12R)-2-((2R,5R,6S)-5-Benzyloxy-5-ethyl-6-methyl-tetrahydro-pyran-2-yl)-15-(4-methoxy-benzyloxy)-2,10,12-trimethyl-1,6,8-trioxa-dispiro[4.1.5.3]pentadec-13-en-9-yl]-hexan-3-one 
• 120269-90-1 C₅₈H₈₆O₁₃ 
• 120297-98-5 Methanesulfonic acid (2S,5S)-2-((S)-1-benzyloxymethyl-propyl)-2-hydroxy-5-((4R,5S)-2,2,5-trimethyl-[1,3]dioxan-4-yl)-hexyl ester 
• 110653-53-7 (2S,3R,4S,7S,8S)-8-benzyloxymethyl-1-(4-methoxybenzyloxy)-2,4-dimethyl-7-methyleneoxydecan-3-ol 

Downstream Products

• 1388822-10-3 C₄₈H₇₅NO₁₀ 
• 1388822-18-1 C₄₉H₇₇NO₁₀ 

Relevant academic research and scientific papers

Antiproliferative Activity of Polyether Antibiotic - Cinchona Alkaloid Conjugates Obtained via Click Chemistry

A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition (click chemistry) of respective N-propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at-ortho position and the least anticancer active derivatives were those substituted at the-para position.

Spectroscopic and computational study of a new isomer of salinomycin

A new derivative of polyether ionophore salinomycin was obtained as a result of a rearrangement catalysed by sulphuric acid in two-phase medium of water/methylene chloride solution. The new isomer was fully characterized by multinuclear 2D NMR, NOESY and MALDI-TOF. The properties of the new compound were additionally study by semiempirical (PM5) and DFT (B3LYP) methods. A potential mechanism of the rearrangement was also proposed.

Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic - Salinomycin

For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic - salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide der

X-ray, FT-IR, NMR and PM5 structural studies and antibacterial activity of unexpectedly stable salinomycin-benzotriazole intermediate ester

The unexpectedly stable benzotriazole ester of salinomycin (SAL-HOBt) - an intermediate product of the amidation reaction of salinomycin has been isolated and structurally characterised (using a single crystal) by X-ray, FT-IR, NMR and semiempirical methods. The results of the X-ray and spectroscopic studies demonstrated that this intermediate ester exist in the solid state and in solution exclusively as the stable O-acyl form. The molecular structure of SAL-HOBt is stabilised by relatively weak intramolecular hydrogen bonds. The PM5 calculation of possible structures of SAL-HOBt has shown that the O-acyl form is more energetically favourable than its N-oxide-N-acyl isomers. The antimicrobial tests show that SAL-HOBt is active against Gram-positive bacteria and clinical isolates methicillin-resistant Staphylococcus aureus (MIC = 1-2 μg/ml).

Synthesis of salinomycin

Salinomycin, a commercially significant coccidiostat isolated from Streptomyces albus, has been synthesised from three principal fragments.Key steps include (a) the use of η3-allylmolybdenum cationic complexes 21a,b for the stereoselective construction of two contiguous stereogenic centres in fragment 5a; (b) the electrophilic cyclisation of 2-(prop-2-ynyl)-2-hydroxyoxanes to give molybdenum and chromium carbene complexes which are precursors to the furan fragment 7; (c) the diastereoselective oxidation of a 1,5-diene with potassium permanganate to generate four stereogenic centres in a single step leading to fragment 8; (d) the oxidative rearrangement of acylfuran 89 en route to the 1,6,8-trioxadispiropentadec-13-ene dispiroacetal core; and finally (e) the use of an allenol ether as an acyl anion equivalent together with the stereoselective hydrolysis of allenol ether intermediate 112 in an alternative synthesis of the dispiroacetal core.

Carbanilide anticoccidials

The present invention is directed to anticoccidial methods, animal feed premixes, and animal feeds, employing a specified carbanilide compound. The present invention is also directed to anticoccidial methods, animal feed premixes, and animal feeds employing the specified carbanilide compound and a polyether antibiotic.

STEREOSELECTIVE SYNTHESIS OF THE MIDDLE (C10-C17) AND RIGHT (C18-C30) SEGMENTS, AND THEIR COUPLING TO COMPLETE A FORMAL SYNTHESIS OF THE POLYETHER ANTIBIOTIC SALINOMYCIN

The middle (C10-C17) and right (C18-C30) segments of the polyether antibiotic salinomycin were stereoselectively synthesized from D-glucose, D-mannitol, and ethyl L-lactate.Coupling of the two segments followed by construction of the bisketal ring system gave the C10-C30 segment, which was already converted to salinomycin by Kishy.