Potential inhibitors of L-asparagine biosynthesis. 3. Aromatic sulfonyl fluoride analogs of L-asparagine and L-glutamine.
The N-[p-(fluorosulfonyl)benzyl] derivatives of L-asparagine and L-glutamine (1a,b) were synthesized as potential inhibitors of L-asparagine synthetase (ASase). Condensation of p-(fluorosulfonyl)benzylamine (2) with the suitably protected amino acid in the presence of dicyclohexylcarbodiimide, followed by deblocking, afforded 1a and 1b. Derivatives 1a and 1b at 10 mM inhibit ASase isolated from Novikoff hepatoma (rats) by 60 and 46%, respectively. Preliminary results on inhibition of Jensen sarcoma (L-asparaginase sensitive) and JA-1 sarcoma (L-asparaginase resistant) tissue cultures by 0.3 mM 1a (139,90%) and 1b (101, 103%), respectively, are discussed.
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D001217:Aspartate-Ammonia Ligase / Q000037:antagonists & inhibitors; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D003864:Depression, Chemical; D005973:Glutamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology; D009374:Neoplasms, Experimental / Q000201:enzymology; D051381:Rats; D012513:Sarcoma, Experimental / Q000378:metabolism; D013450:Sulfones / Q000138:chemical synthesis
D013450:Sulfones; D005973:Glutamine; D001216:Asparagine; D001217:Aspartate-Ammonia Ligase