Inhibition of collagenase by aranciamycin and aranciamycin derivatives.

Abstract

Aranciamycin (1), an anthracycline antibiotic, was found to be an inhibitor of Clostridium histolyticum collagenase, with an IC50 = 3.7 x 10(-7) M. Elastase and trypsin were not inhibited at concentrations less than or equal to 10(-5) M. A number of aranciamycin derivatives 2-13 were prepared and tested for collagenase inhibition. While loss of activity was found for derivatives modified in the sugar ring or rings B and D of the aglycone, increased potency was found when the tertiary alcohol at C-9 was esterified. All compounds 1-13 were found to inhibit DNA synthesis of Yoshida sarcoma tumor cells.

Isolation, Characterization, and Heterologous Expression of the Biosynthesis Gene Cluster for the Antitumor Anthracycline Steffimycin

“…Nevertheless, steffimycin was recently shown to induce a high apoptotic response in HCT116 colon carcinoma cells expressing p53 by inducing DNA damage (12). In addition, steffimycin D derivatives inhibit the growth of ras oncogene-expressed cells (52), steffimycin B analogues containing chemical modification in C-3 are highly active against mouse leukemia P388 cells (57), and aranciamycin derivatives were found to inhibit DNA synthesis of Yoshida sarcoma tumor cells (4).…”

Cloning and Heterologous Expression of the Aranciamycin Biosynthetic Gene Cluster Revealed a New Flexible Glycosyltransferase

“…The anthracycline antibiotic aranciamycin (Scheme ) is produced by S. echinatus and consists of the aglycone aranciamycinone and the sugar 2‐ O ‐methyl‐ L ‐rhamnose 9. Aranciamycin derivatives were found to inhibit the DNA synthesis of Yoshida sacroma tumor cells 10. Interestingly, in contrast to other anthracyclines, aranciamycins are specific collagenase inhibitors, which is interesting for the treatment of nonmalignant diseases.…”

Total synthesis of (–)-spinosyn A

“…The synthesis of 14 began with readily available alcohol 16 (28) (Scheme 6). Glycosidation of 16 with ␣-L-rhamnopyranosyl (Rham) acetate 17 (29) in the presence of tert-butyldimethylsilyl (TBS) trifluoromethanesulfonate afforded the ␣-glycoside 18 in 84% yield. Removal of the tert-butyldiphenylsilyl group with tetrabutylammonium fluoride proceeded in 84% yield, and oxidation of the resulting alcohol under Dess-Martin conditions afforded the corresponding aldehyde in 92% yield (30,31).…”