Possible chemical mechanisms underlying the antitumor activity of S-deoxyleinamycin.
Though less potent than the parent natural product leinamycin, S-deoxyleinamycin displays activity against human cancer cell lines that is comparable to many clinically used agents. The results reported here suggest that the 1,2-dithiolan-3-one heterocycle found in S-deoxyleinamycin reacts with thiols to generate a persulfide intermediate (RSS(-)) that could deliver biologically active polysulfides, hydrogen sulfide, and reactive oxygen species (O2*-, H(2)O(2), and HO*) to the interior of cells.
Sivaramakrishnan
Santhosh
S
Departments of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA.
Gates
Kent S
KS
D000970:Antineoplastic Agents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D007769:Lactams / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry*; D008954:Models, Biological; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry*
C531878:4-hydroxy-4,5,5-trimethyl-1,2-dithiolan-3-one; D000970:Antineoplastic Agents; D007769:Lactams; D018942:Macrolides; D017382:Reactive Oxygen Species; C531876:S-deoxyleinamycin; D013438:Sulfhydryl Compounds; D013440:Sulfides; D013844:Thiazoles; D013871:Thiones; C051552:persulfides; C059000:leinamycin; D004247:DNA