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Biomedical subjects

C Geroni

Publications and source records attributed to C Geroni.

43 records · Page 3Linked to original sources
PubMed1986

Biochemical and biological activity of the anthracycline analog, 4-demethyl-6-O-methyl-doxorubicin.

The chromophore-modified derivative of doxorubicin, 4-demethyl-6-O-methyl-doxorubicin, has been tested for antitumor activity in a range of experimental murine tumor systems. In contrast to the inactive 6-O-methyl derivative of daunorubicin, 4-demethyl-6-O-methyl-doxorubicin provided antitumor effects comparable to that of the parent compound. In addition, detailed DNA-interaction studies showed that the doxorubicin derivative retains the ability to bind DNA by the intercalation mechanism. However, the binding affinity was appreciably reduced following structural modification in the anthraquinone chromophore. On the basis of the proposed models of intercalation, these results could be rationalized in terms of steric influence of the bulky methoxy group. The results of this study are in agreement with the correlation already observed between DNA binding and relative antitumor activity of anthracyclines.

Animals↗
PubMed1986

In vitro studies on anthracycline haloderivatives.

A new class of anthracycline derivatives carrying a halogen atom in the 4' position of the aminosugar moiety was tested in cytotoxicity studies on HeLa cells and on P388 cell lines sensitive and resistant (P388/DX) to doxorubicin, in comparison with the parent drugs doxorubicin (DX) and daunorubicin (DNR). 4'-Haloderivatives of DX generally appear to be more cytotoxic than DX on HeLa, P388 and P388/DX cells. Cellular kinetic studies of DX-haloderivatives on HeLa, P388 and P388/DX cell lines show that they accumulate inside the cell in higher amounts than DX, whereas DNR haloderivatives accumulate in HeLa and P388 cells at levels similar to DNR; only in P388/DX is their accumulation higher as compared with DNR. The results reported suggest that, besides drug accumulation, other factors are involved in the cytotoxic mechanism of action of this class of compounds. Therefore 4'-haloderivatives represent a class of compounds with promising activity, in particular regarding anthracycline-resistant cell lines.

Animals↗
PubMed1981

Biologic activity of daunorubicin linked to proteins via the methylketone side chain.

New daunorubicin-protein conjugates were prepared by covalently linking the antitumor drug to various test proteins via its methylketone side chain. Attachment of daunorubicin to proteins was achieved by nucleophylic substitution reaction of the 14-bromo derivative of the drug, under mild coupling conditions. In contrast to conventional methods, this procedure did not involve reaction or modification of the amino sugar. As expected, the covalent linkage of the drug was generally associated with an appreciable reduction in the drug cytotoxicity to HeLa cells in vitro. The possible advantages of this method for coupling to specific protein carriers are discussed.

Cell Survival↗
PubMedDate not supplied

DNA polymerases and DNA topoisomerases as targets for the development of anticancer drugs.

Studies of a variety of compounds designed as derivatives of prototype active molecules aphidicolin and doxorubicin are reported. So far none of the aphidicolin simpler analogues is as active as the parental molecule. Ten anthracycline analogues, characterized for their cytotoxicity, antitumor activity and inhibition of the relaxing activity of purified human DNA topoisomerase II can be divided into five groups. The majority of the tested compounds shows properties very similar to those of doxorubicin. Epirubicin shows extremely high inhibitory activity toward the relaxing property of topoisomerase II but its antitumor activity and cytotoxicity are similar to those of the former group. The third group includes a compound with extremely high cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity typical of anthracyclines and good antitumor activity but which has no specific inhibitory activity on topoisomerase II. A fifth group includes a totally inactive compound. Our results suggest that the inhibition of human DNA topoisomerase II is only partially correlated with antitumor activity.

Animals↗
PubMedDate not supplied

Synthesis, antitumor activity, and cardiac toxicity of new 4-demethoxyanthracyclines.

The new anthracycline glycosides 4-demethoxy-4'-deoxydaunorubicin and 4-demethoxy-4'-O-methyldaunorubicin, synthesized by coupling 4-demethoxydaunomycinone with 1-chloro-derivatives of protected 4-O-methyl and 4-deoxydaunosamine derivatives, have been converted into the corresponding doxorubicin analogs. The new compounds have been compared for antitumor effect with the parent drugs and with the previously described 4-demethoxydaunorubicin, 4-demethoxy-4'-epidaunorubicin, and their doxorubicin analogs. All of the new analogs were more cytotoxic against HeLa cells in vitro and were more toxic and more potent in mice than the parent drugs. Comparison at optimal antitumor doses showed that the new analogs were as active as the parent drugs against ascitic P388 leukemia and disseminated Gross leukemia. They were also active when administered orally. The new doxorubicin analogs were slightly more active than doxorubicin against ascitic L1210 leukemia and were markedly more active against disseminated L1210 leukemia. In a parallel activity-cardiotoxicity test in C3H mice repeatedly treated iv, 4-demethoxydoxorubicin, 4-demethoxy-4'-epidoxorubicin, 4-demethoxy-4'-O-methyldoxorubicin, and 4-demethoxy-4'-deoxydoxorubicin showed antitumor activity against mammary carcinoma without inducing the typical myocardial lesions observed after doxorubicin treatment, 4-Demethoxy-4'-O-methyldoxorubicin, because of its high antitumor effectiveness, lack of cardiac toxicity in mice, and activity by the oral route, deserves further study.

Animals↗