benzofurans and Fibrosarcoma

First proof to show that (-)-deprenyl/selegiline (DEP), the first selective inhibitor of MAO-B, later identified as the first β-phenylethylamine (PEA)-derived synthetic catecholaminergic activity enhancer (CAE) substance and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP), the tryptamine-derived presently known most potent, selective, synthetic enhancer substance, are specific markers of unknown enhancer-sensitive brain regulations.. Longevity study disclosing the operation of tumor-manifestation-suppressing (TMS) regulation in rat brain. Immonohistochemical identification of a fibromyxosarcoma in rats. Experiments with human medulloblastoma cell lines. Analysis of the mechanism of action of enhancer substances.. Whereas 20/40 saline-treated rats manifested a fibromyxosarcoma, in groups of rats treated with 0.001mg/kg DEP: 15/40 rats; with 0.1mg/kg DEP: 11/40 rats (P<0.01); with 0.0001mg/kg BPAP: 8/40 rats (P<0.001); with 0.05mg/kg BPAP: 7/40 rats (P<0.01) manifested the tumor. Experiments with human medulloblastoma cell lines, HTB-186 (Daoy); UW-228-2, showed that BPAP was devoid of direct cytotoxic effect on tumor cells, and did not alter the direct cytotoxic effectiveness of temozolomide, cisplatin, etoposide, or vincristine. Interaction with distinct sites on vesicular monoamine-transporter-2 (VMAT2) is the main mechanism of action of the enhancer substances which clarifies the highly characteristic bi-modal, bell-shaped concentration-effect curves of DEP and BPAP.. Considering of the safeness of the enhancer substances and the finding that DEP and BPAP, specific markers of unknown enhancer sensitive brain regulations, detected the operation of an enhancer-sensitive TMS-regulation in rat brain, it seems reasonable to test in humans low dose DEP or BPAP treatment against the spreading of a malignant tumor.

Topics: Animals; Antineoplastic Agents; Benzofurans; Brain; Cell Line, Tumor; Dose-Response Relationship, Drug; Fibrosarcoma; Humans; Longevity; Male; Medulloblastoma; Monoamine Oxidase Inhibitors; Rats; Rats, Wistar; Selegiline

A series of novel 1-anilino-4-(arylsulfanylmethyl)phthalazines were designed and synthesized. The structures of all the compounds were confirmed by IR, 1H-NMR, elemental analysis and MS. The analogues 1-(3-chloro-4-fluoroanilino)-4-(3,4- difluorophenylthio-methyl)phthalazine (12) and 1-(4-fluoro-3-trifluoromethylanilino)-4- (3,4-difluorophenyl-thiomethyl)phthalazine (13) showed higher activity than a cisplatin control when tested in vitro against two different cancer cell lines using the microculture tetrazolium method (MTT) method.

Topics: Antineoplastic Agents; Benzofurans; Cell Line, Tumor; Fibrosarcoma; Humans; Liver Neoplasms; Phthalazines

In order to examine the carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran, these two chemicals were subcutaneously administered to Wistar strain male rats at the dose of 80 micrograms, 40 micrograms or 4 micrograms per rat. At sacrifice in two years after the start of the experiment, tumors were observed in the subcutaneous tissue and the liver. Although the number of the rats used is small, the tumor occurrence showed some tendency to relate with the dose of the chemicals given.

Topics: Animals; Benzofurans; Fibroma; Fibrosarcoma; Lipoma; Liver Neoplasms, Experimental; Male; Rats; Rats, Inbred Strains; Skin Neoplasms