Synthesis and cytotoxicity of OLIGOMYCIN (cas 1404-19-9) A derivatives modified in the side chain

Add time:09/02/2019    Source:sciencedirect.com

A novel way of chemical modification of the macrolide antibiotic OLIGOMYCIN (cas 1404-19-9) A (1) at the side chain was developed. Mesylation of 1 with methane sulfonyl chloride in the presence of 4-dimethylaminopyridine produced 33-O-mesyl oligomycin in 56% yield. Reactions of this intermediate with sodium azide produced the key derivative 33-azido-33-deoxy-oligomycin A in 60% yield. 1,3-Dipolar cycloaddition reaction with propiolic acid, methyl ester of propiolic acid, and phenyl acetylene resulted in 33-deoxy-33-(1,2,3-triazol-1-yl)oligomycin A derivatives substituted at N4 of the triazole cycle. The mesylated oligomycin A and 33-deoxy-33-azidooligomycin A did not inhibit F0F1 ATFase ATPase; however, 33-azido-33-deoxy-oligomycin A and the derivatives containing 4-phenyltriazole, 4-methoxycarbonyl-triazole and 3-dimethylaminoethyl amide of carboxyltriazole substituents demonstrated a high cytotoxicity against K562 leukemia and HCT116 human colon carcinoma cell lines whereas non-malignant skin fibroblasts were less sensitive to these compounds. Novel series of oligomycin A derivatives allow for the search of intracellular molecules beyond F0F1 ATP synthase relevant to the cytotoxic properties of this perspective chemical class.

We also recommend Trading Suppliers and Manufacturers of OLIGOMYCIN (cas 1404-19-9). Pls Click Website Link as below: cas 1404-19-9 suppliers

Prev:ReviewModifiers of the OLIGOMYCIN (cas 1404-19-9) sensitivity of the mitochondrial F1F0-ATPase
Next:Original article/Article originalOLIGOMYCIN (cas 1404-19-9)s A and E, major bioactive secondary metabolites produced by Streptomyces sp. strain HG29 isolated from a Saharan soil)