Inhibition of collagenase by aranciamycin and aranciamycin derivatives.
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.
Bols
M
M
Department of Organic Chemistry, Technical University of Denmark, Lyngby.
Binderup
L
L
Hansen
J
J
Rasmussen
P
P
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D051381:Rats; D012513:Sarcoma, Experimental; D013302:Streptomyces / Q000737:chemistry; D014361:Trypsin Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D014361:Trypsin Inhibitors; C075925:aranciamycin; D010196:Pancreatic Elastase; D003012:Microbial Collagenase