In vivo antitumor activity of ilmofosine.

Ilmofosine is a cytostatic/cytotoxic thioether phospholipid derivative. The in vivo anti-tumour activity of this compound was investigated in a methylcholanthrene (MethA)-induced fibrosarcoma and in the 3Lewis-lung carcinoma systems, respectively. Ilmofosine showed antineoplastic and antimetastatic properties at oral doses ranging from 0.

Pharmacokinetics of the thioether phospholipid analogue BM 41.440 in rats.

BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is a cytotoxic thioether phospholipid analogue that recently has entered phase I trials in cancer patients. The objective of this study was to evaluate the pharmacokinetics of this compound in female rats after administration of a single oral dose (15 mg/kg body weight [bw] ).

Synthesis of thioether phosphocholine analogues.

The synthesis of thioether phospholipids, which represent a new class of antitumor agents, is reported here. In particular, the route of synthesis of 3-hexadecylmercapto-2-methoxymethylpropyl-2'-trimethylammoni o-ethyl phosphate (BM 41.440, Ilmofosine), one of the most potent cytostatic/cytotoxic derivatives, is described in detail.

Antineoplastic activity of the thioether lysophospholipid derivative BM 41.440 in vitro.

Thioether lysophospholipid derivatives (TLP) inhibited the in vitro uptake of [3H]thymidine into blasts of eight leukemias and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Cytostatic and cytotoxic effects of TLP were dependent on dosage and incubation time.

BM 41.440: a new antineoplastic, antimetastatic, and immune-stimulating drug.

Alkyllysophospholipids are analogs of the cell membrane component lysophosphocholine. The thioether lysophospholipid BM 41.440 (1-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine) is already in use in phase I and II trials in human cancer therapy.

Ciamexone--a new highly selective immunosuppressive compound.

A local graft versus host reaction between lymphocytes of Balb-c mice and its F-1-generation CB6F1 can be induced because of differences in products of the class II of the major histocompatibility complex (Ir). In this local mixed lymphocyte reaction mainly T-helper cells and B-cells are involved. An induction of a delayed type hypersensitivity reaction with oxazolon significantly decreases the local graft versus host reaction.

Treatment of autochthonous rat colonic adenocarcinomas with a thioether-lysophospholipid derivative in mono- and combination chemotherapy.

In 361 Sprague-Dawley rats autochthonous colorectal carcinomas were induced by intrarectal application of the carcinogen AMMN. Tumor-bearing animals were treated with a synthetic thioether-lysophospholipid (TLP) derivative and in combination chemotherapy with 5-fluorouracil (5-FU) and carmustine (BCNU). There was no difference in the survival time of treated and untreated animals.

Cytotoxicity of thioether-lysophospholipids in leukemias and tumors of human origin.

Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning electron microscopy revealed severe membrane destruction after incubation with thioether-lysophospholipids.

Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids.

Alkyl-lysophospholipids inhibit the growth of Meth A sarcoma cells in vitro. In contrast, murine bone marrow macrophages are not sensitive to the destructive effect of these substances. Since alkyl-lysophospholipids are antimetabolites in the synthesis of 3-sn-phosphatidylcholine, tumor cell destruction can be correlated with the disturbance of this metabolism.