Diallyl sulfides: Selective inhibitors of family X DNA polymerases from garlic (Allium sativum L.)

Food Chem. 2008 May 15;108(2):551-60. doi: 10.1016/j.foodchem.2007.11.007. Epub 2007 Nov 13.

Abstract

Diallyl sulfides, organosulfur compounds isolated from garlic (Allium sativum L.), selectively inhibit the activities of mammalian family X DNA polymerases (pols), such as pol β, pol λ and terminal deoxynucleotidyl transferase (TdT), in vitro. The purified fraction (i.e., Sample-A) consisted of diallyl trisulfide, diallyl tetrasulfide and diallyl pentasulfide (molecular ratio: 5.3:3:1). Commercially purchased diallyl sulfides also inhibited the activities of family X pols, and the order of their effect was as follows: Sample-A>diallyl trisulfide>diallyl disulfide>diallyl monosulfide, suggesting that the number of sulfur atoms in the compounds might play an important structural role in enzyme inhibition. The suppression of human cancer cell (promyelocytic leukaemia cell line, HL-60) growth had the same tendency as the inhibition of pol X family among the compounds. Diallyl sulfides were suggested to bind to the pol β-like region of family X pols.

Keywords: Cytotoxicity; DNA polymerase β (pol β); DNA polymerase λ (pol λ); Diallyl sulfides; Enzyme inhibitor; Family X of DNA polymerases (pol X); Garlic; Pol β-like region; Terminal deoxynucleotidyl transferase (TdT).