Growth Inhibition Activity On K562and Synthesis Studies Of Unsaturated Sulfur-containing Compounds

Unsaturated sulfur-containing compounds (USC) were firstly found in Garlic(Allium sativum L.), including1,2-diallyldisulfide, diallylsulfide,1,3-diallyltrisulfide,1,4-diallyltetrasulfide, allylmethylsulfide,1-allyl-2-methyldisulfide,1-allyl-3-methyltrisulfide,3-vinyl-3,4-dihydro-1,2-dithiine,2-vinyl-4-H-1,3-dithiine,E/Z ajoene and so on.In this paper, unsaturated sulfur-containing compounds and isothiocyanates werestudied in synthetic route, structure-activity relationship and mechanism of growthinhibition on K562cells, the following results were done.1) The unsaturated sulfur-containing compounds in garlic and isothiocyanates weresynthesized successfully, they are3-vinyl-3,4-dihydro-1,2-dithiine,2-vinyl-4-H-1,3-dithiine, allylmethyldisulfide, diallylsulfide,1,2-diallyldisulfide,1,3-diallyltrisulfide,1,3-di(but-3-en-1-yl)trisulfide,1,3-di(pent-4-en-1-yl)trisulfide,1,3-di(hex-4-en-1-yl)trisulfide,1,3-di(2-methylallyl)trisulfide,1,3-di(3-methylbut-2-en-1-yl)trisulfide,1,4-diallyltetrasulfide,4-chlorophenyl isothiocyanate, cyclohexyl isothiocyanate.A enviroment-friendly synthetic protocol of unsaturated thioethers were built byusing water as reaction solvent and phase transfer catalyst.2) The growth inhibition activities of target compounds on K562were determinedwith cell culture technology and MTT assay. The results showed that allexperimental compounds had inhibition activities.1,3-diallyltrisulfide was thebest one of unsaturated sulfur-containing compounds because of its inhibitionrates was67%under25μM, besides, cyclohexyl isothiocyanate was better than4-chlorophenyl isothiocyanate, its inhibition rates was55%under250μM..3) The mechanism of growth inhibition of1,3-diallyltrisulfide and cyclohexylisothiocyanate on K562were studied with Flow Cytometry and AnnexinV-FITC/PI staining. The results showed that the both compounds induced K562 cells apoptosis and differentiate at a low level, and there was no significantimpact in cell cycle. As a result, the exact mechanism of action should be studyfurther.