Synthesis, structural studies, and biological evaluation of some purine substituted 1-aminocyclopropane-1-carboxylic acids and 1-amino-1-hydroxymethylcyclopropanes.
The novel purine derivatives of 1-aminocyclopropane-1-carboxylic acid (8 and 9) and 1-amino-1-hydroxymethylcyclopropane (12 and 13) with methylene spacer between the base and the cyclopropane ring were prepared by multistep synthetic route involving alkylation of adenine and 6-(N-pyrrolyl)purine with 2-hydroxy-methyl-1-aminocyclopropane-1-carboxylic acid derivative 3 as a key reaction. All novel compounds were racemic. The N-9 substitution of the purine ring and the Z-configuration of the cyclopropane ring in 4-13 were deduced from their 1H and 13C NMR spectra by analyses of chemical shifts, H-H coupling constants and connectivities in two-dimensional homo- and heteronuclear correlation spectra. An unequivocal proof of the stereostructure of 1, 4 and 5 was obtained by their X-ray structure analysis. The novel compounds were evaluated on cytostatic and antiviral activities in several cell lines. The 6-(N-pyrrolyl)purine derivative of 1,2-aminocyclopropane alcohol 12 exhibited a more pronounced inhibitory activity against the proliferation of cervical carcinoma (HeLa) and human fibroblast (WI-38) cells than other types of tumor cell lines. None of the compounds showed inhibitory activities against cytomegalovirus, varicella-zoster virus or other viruses.
Dzolić
Zoran
Z
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Zagreb, Croatia.
Kristafor
Vedran
V
Cetina
Mario
M
Nagl
Ante
A
Hergold-Brundić
Antonija
A
Mrvos-Sermek
Draginja
D
Burgemeister
Thomas
T
Grdisa
Mira
M
Slade
Neda
N
Pavelić
Kresimir
K
Balzarini
Jan
J
De Clercq
Erik
E
Mintas
Mladen
M
D000596:Amino Acids / Q000737:chemistry; D000598:Amino Acids, Cyclic / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003521:Cyclopropanes / Q000737:chemistry*; D005260:Female; D006801:Humans; D051379:Mice; D011687:Purines / Q000737:chemistry*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003521:Cyclopropanes; D011687:Purines; C023863:1-aminocyclopropane-1-carboxylic acid