olivomycins and Melanoma

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

A total of 66 experiments were performed with a purpose of studying the effect of olivomycin on the melanoblastoma cells of the human eye vascular tract. Heterotransplants of the human eye vascular tract melanoblastoma in the anterior chamber of the rabbit eye served the objects of the studies. Olivomycin was used in 34 out of 66 experiments and 32 experiments were control. Separate tumor cells together with pronounced signs of necrosis were detected on histological examination only in 1 out of 34 transplants treated with olivomycin. The transplants in the other 33 experiments resolved. The transplant in the control experiments consisted of viable cells at the same period. On the basis of the experiments it was concluded that olivomycin had a pronounced destroying effect on melanoblastoma cells under conditions of heterotransplantation and may be recommended for clinical use for prophylaxis of metastasis in post-operative periods.

Topics: Animals; Drug Evaluation, Preclinical; Eye; Eye Neoplasms; Humans; Melanoma; Neoplasm Transplantation; Neoplasms, Experimental; Olivomycins; Rabbits

Topics: Animals; Antineoplastic Agents; Autoradiography; Cyclophosphamide; Drug Therapy, Combination; Histocytochemistry; Injections, Intraperitoneal; Injections, Intravenous; Leukocyte Count; Melanoma; Mice; Neoplasms, Experimental; Olivomycins; Organophosphorus Compounds; Prednisolone; Radiation-Sensitizing Agents; Time Factors; Tritium; Vitamin K

Topics: Animals; Anterior Chamber; Antibiotics, Antineoplastic; Choroid Neoplasms; Humans; Melanoma; Melphalan; Neoplasm Transplantation; Olivomycins; Rabbits; Thiotepa

Topics: Adult; Antibiotics, Antineoplastic; Dactinomycin; Female; Flavonoids; Humans; Leukopenia; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Olivomycins; Radiation-Sensitizing Agents; Skin Neoplasms

Topics: Animals; Antibiotics, Antineoplastic; Dactinomycin; Male; Melanoma; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Olivomycins; Rats; Sarcoma; Sarcoma 37

Topics: Animals; Antibiotics, Antineoplastic; Dactinomycin; Male; Melanoma; Mice; Neoplasm Transplantation; Neoplasms, Experimental; Olivomycins; Rats; Sarcoma

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Melanoma; Mice; Neoplasms; Neoplasms, Experimental; Olivomycins; Pharmacology; Research

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Dysgerminoma; Female; Fibrosarcoma; Humans; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Melanoma; Neoplasms; Olivomycins; Ovarian Neoplasms; Sarcoma; Stomach Neoplasms; Uterine Cervical Neoplasms