1. Antitumor and antiinflammatory agents: N-benzoyl-protected cyanomethyl esters of amino acids
Z Sajadi, M Almahmood, L J Loeffler, I H Hall J Med Chem. 1979 Nov;22(11):1419-22. doi: 10.1021/jm00197a027.
A series of N-protected cyanomethyl esters of various amino acids was synthesized and tested for antineoplastic and antiinflammatory activity in rodents. Utilizing the L-phenylalanine cyanomethyl ester and varying the N-protecting moiety demonstrated that the N-tosyl and the N-Cbz analogues were the most active against Ehrlich ascites cell proliferation. The N-(carbobenzyloxy)- and N-benzoyl-L-phenylalanine cyanomethyl esters were the most active against carrageenan-induced inflammation. In the N-benzoyl series of cyanomethyl esters, L-alanine, DL-valine, and L-leucine amino acid analogues were the most active against Ehrlich ascites cell proliferation. The glycine and L-alanine analogues possessed the best inhibitor activity in the antiinflammatory screen. The cyanomethyl esters also demonstrated immunosuppressive activity and the ability to suppress the writhing reflex which is associated with inflammatory pain. However, no antipyretic or narcotic analgesic activity was demonstrated by these agents.
2. Studies on the absorption of the pancreatic function test peptide, N-benzoyl-L-tyrosyl-p-aminobenzoic acid, and related compounds by isolated rat small intestine
M L Gardner, C J Mitchell Q J Exp Physiol. 1981 Jan;66(1):17-24. doi: 10.1113/expphysiol.1981.sp002525.
The peptide, N-benzoyl-L-tyrosyl-p-aminobenzoic acid, which is used in an oral test of pancreatic function, has been perfused through isolated rat small intestine in order to determine whether it can be absorbed across the intestine in intact form, and whether it is hydrolysed appreciably by intestinal enzymes. For comparison, transport of N-benzoyl-DL-tyrosine, L-tyrosine, L-tyrosyl-L-leucine and p-aminobenzoic acid has also been studied. Very small amounts of bound tyrosine (probably mainly intact peptide plus some benzoyl-tyrosine) and of free p-aminobenzoic acid crossed the intestine during perfusion with N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Adsorbed pancreatic enzymes were possibly responsible for the very small amount of hydrolysis of the peptide. However, no detectable free tyrosine crossed the intestine during perfusion with N-benzoyl-L-tyrosyl-p-aminobenzoic acid or with N-benzoyl-DL-tyrosine. In contrast, substantial quantities of free tyrosine crossed the intestine during perfusion with L-tyrosine or with L-tyrosyl-L-leucine. Net transport of tyrosine from L-tyrosyl-L-leucine was less than that from equimolar free L-tyrosine; no detectable intact L-tyrosyl-L-leucine crossed the intestine. During perfusion with free p-aminobenzoic acid the concentration in the serosal secretion apparently exceeded that in the lumen by a factor of 1.7; this suggests active transport of p-aminobenzoic acid.
3. Synthesis and biological activity of novel amino acid-(N'-benzoyl) hydrazide and amino acid-(N'-nicotinoyl) hydrazide derivatives
Sherine N Khattab Molecules. 2005 Sep 30;10(9):1218-28. doi: 10.3390/10091218.
The coupling reaction of benzoic acid and nicotinic acid hydrazides with N- protected L-amino acids including valine, leucine, phenylalanine, glutamic acid and tyrosine is reported. The target compounds, N-Boc-amino acid-(N;-benzoyl)- and N- Boc-amino acid-(N;-nicotinoyl) hydrazides 5a-5e and 6a-6e were prepared in very high yields and purity using N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl- methylene]-N-methyl-methanaminium hexafluorophosphate N-oxide (HATU) as coupling reagent. The antimicrobial activity of the Cu and Cd complexes of the designed compounds was tested. The products were deprotected affording the corresponding amino acid-(N;-benzoyl) hydrazide hydrochloride salts (7a-7e) and amino acid-(N;- nicotinoyl) hydrazide hydrochloride salts (8a-8e). These compounds and their Cu and Cd complexes were also tested for their antimicrobial activity. Several compounds showed comparable activity to that of ampicillin against S. aureus and E. coli.
