- Antiproliferative Activity of Polyether Antibiotic - Cinchona Alkaloid Conjugates Obtained via Click Chemistry
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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.
- Skiera, Iwona,Antoszczak, Micha?,Trynda, Justyna,Wietrzyk, Joanna,Boratyński, Przemys?aw,Kacprzak, Karol,Huczyński, Adam
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p. 911 - 917
(2015/10/06)
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- Synthesis, anticancer and antibacterial activity of salinomycin N-benzyl amides
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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.
- Antoszczak, Michal,Augustynowicz-Kope, Ewa,Brzezinski, Bogumil,Huczyski, Adam,Maj, Ewa,Wietrzyk, Joanna,Napirkowska, Agnieszka,Stefaska, Joanna,Janczak, Jan
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p. 19435 - 19459
(2015/03/13)
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- Spectroscopic and computational study of a new isomer of salinomycin
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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.
- Pankiewicz, Rados?aw
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p. 464 - 470
(2013/10/22)
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- Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic - Salinomycin
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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
- Huczynski, Adam,Janczak, Jan,Stefanska, Joanna,Antoszczak, Michal,Brzezinski, Bogumil
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experimental part
p. 4697 - 4702
(2012/08/13)
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- X-ray, FT-IR, NMR and PM5 structural studies and antibacterial activity of unexpectedly stable salinomycin-benzotriazole intermediate ester
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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).
- Huczyński, Adam,Janczak, Jan,Antoszczak, Micha?,Stefańska, Joanna,Brzezinski, Bogumil
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experimental part
p. 197 - 203
(2012/10/07)
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- Synthesis of salinomycin
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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.
- Kocienski, Philip J.,Brown, Richard C. D.,Pommier, Agnes,Procter, Martin,Schmidt, Bernd
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- Carbanilide anticoccidials
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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.
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- 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
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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.
- Horita, Kiyoshi,Nagato, Satoshi,Oikawa, Yuji,Yonemitsu, Osamu
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p. 3253 - 3256
(2007/10/02)
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