Antiproliferative Activity of Spirocyclic Cyclodipeptides, Derivatives of 1-amino-3-methyl-1-cyclohexanecarboxylic Acid

Jarmila Vinšová¹ (vinsova@faf.cuni.cz), Karel Kosař², Evžen Kasafírek³, Antonín Šturc³, Jiří Taimr³

¹Department of Inorganic and Organic Chemistry, and
²Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
³Research Institute for Pharmacy and Biochemistry, Kouřimská 17, Prague, Czech Republic

Summary

Spirocyclic cyclodipeptides of the general formula cyclo(A-B) where A is L(D) amino acid (Gly, Ala, Ser, Leu, Val, Pgl, Phe) and B is r-1-amino-t-3-methyl-1-cyclohexanecarboxylic acid, were prepared; the aim was to determine how the substitution of methyl in position 3 of the cyclohexane circle would influence the inhibition of the proliferative activity of the caudal morphogenetic system (CMS) of chick embryos. Spirocyclic cyclodipeptides 1(a-l) have been prepared by cyclization of the corresponding linear dipeptide methyl esters 2(a-l) which were obtained by condensation of protected amino acids by DCCI method. The results of CHEST I tests show a lower activity in the series tested, as compared with the derivatives without methyl in position 3 of the cyclohexyl ring. A significant retardation of growth has been shown only by cyclo(D-Val-3-Me-Ach).