6-(2,4-Dinitrophenyl)-mercaptopurine, a stronger immunosuppressive drug than 6-mercaptopurine to primary humoral T-cell dependent immune response in mice]

The suppressive effect of 6-(2,4-Dinitrophenyl)-mercatopurine (DNP-MP) and 6-mercaptopurine (MP) was investigated on the early primary immune response of mice against the T-cell dependent antigens DNP49-bovine gamma globuline (BGG), sheep red blood cells (SRBC) or FITC8-BCG and the T-cell independent DNP22-Ficoll. The number of IgM antibody forming cells (AbFC) to the hapten determinants and to the SRBCs per 10(6) spleen cells was determined. DNP-MP reduced the number of AbFCs after the immunisation with the T cell dependent antigens always stronger than the MP, independently of the antigen type by which the mice had been immunised. The Anti-DNP22-Ficoll immune response was suppressed equally by both immunosuppressive drugs. DNP-MP is not a specific immunosuppressive drug for the anti-DNP-B-lymphocytes. Helper T-cells and macrophages are discussed as target cells for the stronger unspecific action of DNP-MP.     

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.