Synthesis And Characterization Of Anticancer Temozolomide Coupled With Nitric Oxide Donors

Nitric oxide (NO) is an important biological second messenger and functional molecule, which is involved in numerous physiological and pathological processes. Several studies have also shown that the NO through NO donors in vivo is cytotoxic to tumor cells leading to apoptosis, mainly involving preventions of tumor cells'proliferation and transition which indicated that NO donors have promising potentialities in anticancer therapy. As an anti-encephaloma drug, temozolomide can effectively improve the life quality of the patients, but it can't prolong the patients'life universally, especially some patients with encephaloma have no reaction with temozolomide, therefore, we incorporate NO-donor compounds with temozolomide through which changing its structure of branch in order to get more effective anticancer drugs.We synthesized four kinds of NO-donor ramification of temozolomide nitric acid estersI1~3 according to catalyzing amide to carboxylic acide in H2SO4, then through Nucleophilic Substitution reaction, we got the single substitute bromine alkyl esters, which reacted with AgNO3 to come out the target compounds. temozolomide nitric acid estersI4 was systhesized through anther reaction rount, which react bromine alcohol with temozolomide chloride, then reacted with AgNO3 to come out the target compound.In the preparation of target compounds II, on account of the long route, we synthesized benzenesulfonyfuroxan (benzensulfonicfuroxan) firstly, and then got the target compounds through Schotten-Baumann reaction. Beside that, we changed the order of putting materials and some solvent in some reactions, which resulted in improvement of products. As an anti-encephaloma drug, temozolomide can effectively improve the life quality of the patients, but it can't prolong the patients'life universally, especially some patients with encephaloma have no reaction with temozolomide, therefore, we incorporate NO-donor compounds with temozolomide through which changing its structure of branch in order to get more effective anticancer drugs.We totally synthesized 9 novel compounds, and all of them have been characterized through 1H-NMR, MS, IR and elemental analysis.