Affinity therapeutics. 1. Selective incorporation of 2-thiouracil derivatives in murine melanomas. Cytostatic activity of 2-thiouracil arotinoids, 2-thiouracil retinoids, arotinoids, and retinoids

Abstract

The incorporation of 2-[35S]thiouracil and two of its derivatives into murine melanomas, in vivo, was studied. It was confirmed [J. R. Whittaker, J. Biol. Chem., 246, 6217--6226 (1971)] that 2-thiouracil has a marked affinity for melanin-producing tissue and that an affinity for such tissue could be sustained by 5-substituted 2-thiouracils. A series of derivatives of arotinoids and retinoids, with or without a 2-thiouracil group as a potential carrier to obtain affinity for melanomas, was examined for cytostatic activity, in vitro. None of these showed significant activity against murine melanomas.

A Static Picture of the Relaxation and Intersystem Crossing Mechanisms of Photoexcited 2-Thiouracil

“…Interestingly, a side effect of 6TG treatment is an 100-fold increase in the incidence of skin cancer, which has been attributed to its very different photochemistry − in comparison with guanine. Similarly, 2-thiouracil (2TU) has been historically used as an antithyroid drug (6- n -propyl-2-thiouracil is currently listed as essential by the WHO) and has shown some potential for the development of cytostatika, heavy-metal antidotes, or photosensitizers for photodynamical therapy . As with 6TG, the different photophysics and photochemistry of 2TU in comparison with uracil could lead to significant side effects in potential medical applications of 2TU.…”

Designing Prodrugs and Bioprecursors

“…77 The 2,3-dichlorophenoxyacetic moiety of ethacrynic acid was claimed to have a high affi nity for renal tissue, 78 and 2-thiouracil and 6-propylthiouracil exhibit marked affi nities for melatonin-producing tissues. 81 Many other examples of selective conducting moieties are found in X-ray contrast media and radioisotope imaging agents. 81 Many other examples of selective conducting moieties are found in X-ray contrast media and radioisotope imaging agents.…”

Synthesis of Pyrimidine, Thiazolopyrimidine, Pyrimidotriazine and Triazolopyrimidine Derivatives and their Biological Evaluation

“…Chart 1). In continua tion to our previous work [5] and due to the re ported biological activity [6][7][8][9] we were stim ulated to synthesize more derivatives of this ring system. Compounds 3 and 5 were taken as the re active starting materials for the present study, ow ing to the presence of more than one active site in both of them.…”