olivomycins and Lymphoma

A novel way of chemical modification of the antibiotic olivomycin A (1) at the side chain of the aglycon moiety was developed. Interaction of olivomycin A with the sodium periodate produced the key acid derivative olivomycin SA (2) in 86% yield. This acid was used in the reactions with different amines in the presence of benzotriazol-1-yl-oxy-trispyrrolidino-phosphonium hexafluorophosphate (PyBOP) or diphenylphosphoryl azide (DPPA) to give corresponding amides. Whereas olivomycin SA was two orders of magnitude less cytotoxic than the parent antibiotic, the amides of 2 demonstrated a higher cytotoxicity. In particular, N,N-dimethylaminoethylamide of olivomycin SA showed a pronounced antitumor effect against transplanted experimental lymphoma and melanoma and a remarkably high binding constant to double stranded DNA. The therapeutic effects of this derivative were achievable at tolerable concentrations, suggesting that modifications of the aglycon's side chain, namely, its shortening to methoxyacetic residue and blocking of free carboxyl group, are straightforward for the design of therapeutically applicable derivatives of olivomycin A.

Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Cell Proliferation; DNA; Female; Humans; Lymphoma; Melanoma; Mice; Olivomycins

Lymphadenosis NK/LY resistant to rubomycin was obtained on its repeated cultivation in mice treated with the antibiotic. The rubomycin resistance was stable and preserved for a long period of time when the line was repeatedly cultivated in mice not exposed to the antibiotic. The tumor cells resistant to rubomycin acquired resistance to olivomycin. DNA histograms of the tumor cells obtained by means of impulse cytophotometry provided determination of the tumor sensitivity and resistance to antitumor agents. It is recommended that impulse cytophotometry be used for the screening of antitumor drugs and development of their administration regimen.

Topics: Animals; Cell Line; Daunorubicin; DNA, Neoplasm; Dose-Response Relationship, Drug; Drug Resistance; Lymphoma; Male; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Olivomycins; Time Factors

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Line; Cyclophosphamide; Flavonoids; Lymphoma; Mice; Nitrogen Mustard Compounds; Olivomycins; Phosphines; Thiotepa; Uracil

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Depression, Chemical; Drug Synergism; Leukocytes; Lymphoma; Mice; Mononuclear Phagocyte System; Neoplasms, Experimental; Olivomycins; Peritoneal Cavity; Phagocytosis; Polysaccharides, Bacterial; Serratia marcescens; Stimulation, Chemical

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Lymphoma; Lymphoma, Non-Hodgkin; Mice; Neoplasms; Olivomycins; Pharmacology; Research; Sarcoma; Sarcoma, Experimental

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Carcinoma; Dactinomycin; Lymphoma; Neoplasms; Neoplasms, Experimental; Olivomycins; Pharmacology; Rats; Research; Sarcoma; Sarcoma, Experimental

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Busulfan; Carcinoma, Ehrlich Tumor; Leukemia; Leukemia, Myeloid; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Sarcoma 180; Thiotepa; Toxicology

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Chemistry, Pharmaceutical; Lymphoma; Lymphoma, Non-Hodgkin; Mice; Neoplasms; Olivomycins; Pharmacology; Research; Sarcoma; Sarcoma, Experimental; Toxicology

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antineoplastic Agents; Busulfan; Cytostatic Agents; Lymphoma; Lymphoma, Non-Hodgkin; Mercaptopurine; Methylthiouracil; Mice; Neoplasms, Experimental; Nitrogen Mustard Compounds; Olivomycins; Pharmacology; Research; Thiotepa