thiouracil and Lung-Neoplasms

The condensation of 6-amino-2-thiouracil 1 with aromatic aldehydes afforded azomethine derivatives 3a,b. The formed azomethines underwent [4+2] cycloaddition with enaminones 4a-c and enaminonitrile 9 to form the corresponding condensed pyrimidines 8a-f and 11a,b, respectively. On the other hand, the interaction of 3a,b with acetylene derivatives 12a,b, 14 afforded the corresponding pyrido[2,3-d]pyrimidines 13a-d and 16a,b, respectively. The newly synthesized 2-azadiene 18 reacted with ortho-aminophenol and ortho-aminothiophenol 19a,b to yield the amidines 21a,b. The in vitro antimicrobial activity of some of the newly synthesized compounds was examined. All the tested compounds proved to be active as antibacterial and antifungal agents. Also the in vivo antitumor activity of compounds 8a, 11b, 13a,d, and 16b against lung (H460) and liver (HEPG2) carcinoma cells was examined. Compounds 8a, 16b showed moderate activity against lung carcinoma cell line (H460).

Topics: Antifungal Agents; Antineoplastic Agents; Drug Screening Assays, Antitumor; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Liver Neoplasms; Lung Neoplasms; Microbial Sensitivity Tests; Molecular Structure; Pyrimidines; Structure-Activity Relationship; Thiouracil; Tumor Cells, Cultured

The uptake and retention of 14C-thiouracil and 125I-thiouracil in small lung metastases of B16 murine melanoma was studied in beige mice injected intravenously with melanoma cells. By impulse counting of excised tumor and organ pieces, a high concentration of radioactivity was found in the lung metastases, as compared to normal tissues. The highest tumor/organ concentration ratios appeared 24 h after injection of the radiolabeled thiouracil. A separate autoradiographic study on the disposition of 14C-thiouracil in mice with melanoma metastases confirmed the impulse counting results and also showed the absence of any other site of retention of radioactivity except for hair follicles and to some extent the thyroid. The selective uptake of 14C- and 125I-thiouracil in melanomas depends on their acceptance as false melanin precursors, making them specific markers for growing melanin. The results indicate that radiolabeled thiouracil may be useful for clinical diagnosis and, possibly, therapy of malignant melanotic melanomas.

Topics: Animals; Lung Neoplasms; Male; Melanins; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Thiouracil; Tissue Distribution