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Biomedical subjects

K Dzierzbicka

Publications and source records attributed to K Dzierzbicka.

12 recordsLinked to original sources
PubMed2006

Immunomodulatory properties of new conjugates of muramyl dipeptide and nor-muramyl dipeptide with retro-tuftsin (Arg-Pro-Lys-Thr-OMe).

Six new conjugates of muramyl dipeptide and nor-muramyl dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFalpha--tumour necrosis factor alpha, IL6--interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of muramyl dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFalpha. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2006

Synthesis of analogues of anthraquinones linked to tuftsin or retro-tuftsin residues as potential topoisomerase inhibitors.

A novel group of [(4-, 5- or 8)-hydroxy-9,10-anthraquinone-1-yl]-(tuftsin or retro-tuftsin) acids and methyl esters has been synthesized as potential anticancer compounds. The corresponding protected tuftsin or retro-tuftsin derivatives were also synthesized. We hope that combining compounds of different mechanisms of action will improve their clinical properties, and that our new analogues will be much more effective against multidrug-resistant tumour cell lines.

Anthraquinones↗
PubMed2005

Synthesis and biological activity of tuftsin, its analogue and conjugates containing muramyl dipeptides or nor-muramyl dipeptides.

Several conjugates of muramyl dipeptide (MDP) or nor-muramyl dipeptide (nor-MDP) with tuftsin were synthesized. Conjugates 8a-f were prepared by acylation of protected tuftsin with the isoglutamine carboxyl group of MDP or nor-MDP 2a-f. Also tuftsin analogue 6 (H-Thr-Lys-Pro-Arg(NO2)-OH) was obtained. All synthesized compounds were investigated at the Medical University of Gdansk. The biological activity of the examined compounds was estimated using in vitro cultures of human monocytes and lymphocytes. The substances displayed cytotoxic effects, as was revealed in the viability tests performed. The effects were most probably mediated by the induction of an oxidative burst in monocytes and the stimulation of redox enzymes in lymphocytes. In addition, the analogues turned out to be efficient stimulators of TNFalpha and IL6 secretion by monocytes and lymphocytes. Nevertheless, the secretion of cytokines did not affect the viability of the leukocyte population used in the experiments.The beneficial properties of the compounds examined (mainly 6, 3, 8a and 8c), which implies their usefulness as potential therapeutic agents, are connected with their rapid start of action and more efficient effects compared with tuftsin alone. An in vivo assay on animal models will be performed.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Biological activity of conjugates of muramyl dipeptides with batracylin derivatives.

Antitumour activity of batracylin (BAT), muramyldipeptide (MDP) and four immunomodulatory conjugates of BAT with MDP were evaluated in the study. The activity was assessed using viability tests performed in the cultures of tumour cell lines of different tissue origin such as WEHI 164 (fibrosarcoma), K562 (leukaemia), and Ab (melanoma), populations of immune cells isolated from peripheral blood, and the tumour cells mixed with immune cells. An intensity of cell death caused by the analogues was measured using flow cytometry analysis as subG1 peak and the distinction between necrotic and apoptotic DNA cleavage during cell death was performed using DNA fragmentation assay. The compounds 11c, 11e and 11h managed to kill WEHI 164 cells in the presence of immune cells in apoptotic manner while BAT and conjugate 11a caused necrosis at the same time. Necrotic pattern of DNA cleavage was also noted in all cultures containing K562 and Ab cells. BAT and MDP caused necrosis in the cultures of pure immune cells, while the conjugates did not affect these cultures at all. Surprisingly, some analogues increased viability of K562 and Ab cells. Low toxicity and ability to induce apoptosis suggested usefulness of some analogues, mainly 11c, as antitumour drugs in limited range of tumours of certain tissue origin, such as WEHI 164.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2001

Synthesis and antitumor activity of conjugates of muramyldipeptide, normuramyldipeptide, and desmuramylpeptides with acridine/acridone derivatives.

The synthesis of two groups (Chart 1, types A and B) of conjugates of MDP (muramyldipeptide) and nor-MDP (normuramyldipeptide) with acridine/acridone derivatives and the synthesis of analogues of desmuramylpeptides (Chart 1, types C and D) containing acridine/ acridone derivatives have been described. In type A conjugates, the hydroxyl group at C6 of the sugar moiety was acylated with acridine/acridone N-substituted omega-aminoalkanocarboxylic acids (Scheme 1), whereas the conjugates of type B (Table 2) and three analogues of type C or D (Scheme 2) have an amide bond formed between the carboxylic group of isoglutamine and the amine function of the respective acridine/acridone derivatives. The preliminary screening data indicate that the analogues of groups A, C, and D exhibit small cytotoxic activity, whereas several analogues of type B, 4b, 4c, 4e, 4g, 4h, 4i, and 4l, exhibiting potent in vitro cytotoxic activity against a panel of human cell lines (Table 4), have been selected by the National Cancer Institute (NCI) Evaluation Committee for further testing. Analogues 4b and 4h were active in the in vivo hollow fiber assay (Table 5). Analogue 3a shows an immunostimulating effect on the cytotoxic activity of the NK cells obtained from the spleen of healthy and Ab melanoma bearing animals.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

The in vitro effect of new muramyl peptide derivatives on cytotoxic activity of NK (natural killer) cells from hamsters bearing Ab Bomirski melanoma.

The modulation of NK activity by muramyl dipeptides derivatives against Ab (amelanotic) Bomirski melanoma and human erythroleukemia K562 cells was studied in vitro. The stimulatory effect was observed for 3 of 7 muramyl dipeptides: MDP(L-Ala)C921, MDPC857 and L18-MDP(Ala) in relation to cytotoxic activity of NK cells obtained from peripheral blood and spleen of healthy and Ab Bomirski melanoma bearing hamsters. An increased of cytotoxic activity NK cells isolated from animals before and during the transplantable phase of the tumor against K562 was found. A similar stimulation was received for NK cells obtained from animals against their own melanoma cells. The most significant influence of examined MDP derivatives on the cytotoxic activity of NK cells were obtained from animals between 10 to 12 days of tumor growth. The extent of the modulation of cytotoxic activity of NK cells was dependent on its initial value both in healthy control and Ab Bomirski melanoma bearing hamsters. If natural cytotoxic activity was high the stimulatory effect of the examined MDP derivatives was only slightly expressed.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

[L-MTP-PE--a potential antineoplastic agent].

Muramyl tripeptide phosphatidylethanolamine (MTP-PE), a synthetic lipophilic analogue of muramyl dipeptide, stimulates monocytes/macrophages to kill a variety of tumor cells in vitro and in vivo. Encapsulation of MTP-PE into multilamellar liposomes (L-MTP-PE) was specifically designed for in vivo targeting to macrophages by i.v. infusion and is the only form of the drug currently available for clinical trials (CGP 19835A Lipid). L-MTP-PE is presently undergoing clinical trials in patients with recurrent osteosarcoma and melanoma. L-MTP-PE combined with other anticancer agents may thus improve long-term cure rates of patients with this diseases.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

[Muroctasin, a muramyl dipeptide derivative].

This paper presents a review of studies on the metabolism, pharmacological and clinical properties of a new synthetic muramyl dipeptide derivative N2-/(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl/-N6-stearoyl-L-lysine(MD P- Lys(L18), muroctasin). Due to its effect on the number of peripheral blood leukocytes this compound is expected to be a useful drug for the treatment of leukopenia induced by cancer chemotherapy or radiation therapy.

Acetylmuramyl-Alanyl-Isoglutamine↗