A library of novel 2-(het)arylpyrrolidine-1-carboxamides were obtained via a modular approach based on the intramolecular cyclization/Mannich-type reaction of N-(4,4-diethoxybutyl)ureas. Their anti-cancer activities both in vitro and in vivo were tested. The in vitro activity of some compounds towards M-Hela tumor cell lines was twice that of the reference drug tamoxifen, whereas cytotoxicity towards normal Chang liver cell did not exceed the tamoxifen toxicity. In vivo studies showed that the number of surviving animals on day 60 of observation was up to 83% and increased life span (ILS) was up to 447%. Additionally, some pyrrolidine-1-carboxamides possessing a benzofuroxan moiety obtained were found to effectively suppress bacterial biofilm growth. Thus, these compounds are promising candidates for further development both as anti-cancer and anti-bacterial agents.

The reactions of glycine hydroxamic and DL alanine hydroxamic acids with triacetonamine are chemoselective and afford 1 hydroxy 7,7,9,9 tetramethyl 1,4,8 triazaspiro[4.5]decan 2 one (3) and (±) 1 hydroxy 3,7,7,9,9 pentamethyl 1,4,8 triazaspiro[4.5]decan 2 one (4), re spectively. The X ray diffraction study showed that compound 3 crystallizes as a solvate with MeCN (1 : 1). As shown by ESR measurements, spiro hydroxamic acids 3 and 4 are NO donors in in vitro biological systems. The NO donor activity of compounds 3 and 4 was found to be substantially higher in the presence of DMSO. Homologue 4 is a stronger NO donor than 3. Compound 4 also exhibits high antimetastatic activity (81%) on the B16 melanoma model.

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It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

Acylation of cis,trans,cis Pt IV (RNH 2 )(NH 3 )(OH) 2 Cl 2 with acetic anhydride afforded com plexes cis,trans,cis Pt IV (RNH 2 )(NH 3 )(OAc) 2 Cl 2 , where R is 2,2,6,6 tetramethyl 1 oxyl piperidin 4 yl (1b) or 2,2,5,5 tetramethyl 1 oxylpyrrolidin 3 yl (2b). The complexes were characterized by elemental analysis, HPLC, and IR, UV, and ESR spectra. Complex 1b exhibits high antitumor activity comparable with that of Cisplatin against leukemia P388 used as the experimental tumor. Simultaneous administration of low doses of 1b and Cisplatin (1/20 of LD 50 each) results in synergism of the antitumor activity and 100% cure of animals.