Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid.

Background: Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant, it also possesses anticancer activity. MPA acts as Inosine-5'-Monophosphate Dehydrogenase (IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too.

Immunosuppressive properties of amino acid and peptide derivatives of mycophenolic acid.

Mycophenolic acid (MPA) was coupled with amino acids and biologically active peptides including derivatives of tuftsin to modify its immunosuppressive properties. Both amino acid unit in the case of simple MPA amides and modifications within peptide moiety of MPA - tuftsin conjugates influenced the observed activity. Antiproliferative potential of the obtained conjugates was investigated in vitro and MPA amides with threonine methyl ester and conjugate of MPA with retro-tuftisin occurred to be more selective against PBMC in comparison to parent MPA.

Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid.

The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group.

Tuftsin - Properties and Analogs.

Background: Immunomodulation is one of the significant therapeutic strategies. It includes both stimulation and suppression of the immune system by a variety of substances called immunomodulators, designed to regulate the immune response of the organism against infections of varying etiology. An example of such a substance is tuftsin (TKPA) 3 (Fig.

New Analogues of Mycophenolic Acid.

Background: Mycophenolic acid (MPA) possesses antibacterial, antifungal, antiviral, immunosuppressive and anticancer properties. It is a non-competitive and reversible inhibitor of dehydrogenase inosine-5'-monophosphate (IMPDH). This compound belongs to the immunosuppressive drugs used for the prevention of both acute and chronic transplant rejection.

New conjugates of mycophenolic acid and their antiproliferative activity.

The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N(6)-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a-h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity.

Synthesis of Combretastatin A-4 Analogs and their Biological Activities.

Combretastatin A-4 (CA-4) is a natural product, which consists of two phenyl rings, linked by an ethylene bridge. CA-4, inhibitor of polymerization of tubulin to microtubules, possesses a strong antitumor and anti-vascular properties both in vitro and in vivo. Previous studies showed that disodium phosphate salt of CA-4, a water-soluble prodrug is well tolerated at therapeutically useful doses.