Synthesis Of Targeting Microwave Hyperthermia Sensitizers And Preliminary Studies Of Their Biological Activities

Based on the relationship between molecular structure of a chemical and ability of absorbing microwave energy, targeting microwave hyperthermia sensitizers, aimed to be used in the treatment of tumor, were designed and synthesized in this study.We carry out our research work on the following six aspects: First, obtaining chemicals or anti-cancer drugs that can absorb microwave energy strongly by determining the efficient dielectric constants (ε_eff) and find out minimum efficient concertration (C_min). Second , in order to demonstrate the possible efficacy doesn't contribute to the inherent cytotoxicity of the sensitizers, it is necessary to exclude the possibility that the sensitizers have cytotoxicity by adding the thermosensitizers to the culture of Hela cells and Hep2 cells at 37℃ and finding out the maximal non-cytotoxic concentration (C_max), selecting the innocuous chemicals to tumor cells as thermosensitizer if C_max >C_min .Third, the actual efficacies of the sensitizers at C_max are evaluated in vitro by livability analysis of Hela cells and Hep2 cells after exposing to microwave at a power density of 0.18-0.2 mW/cm² for 2.5min. Fourth, synthesis of sensitizers 24a-c and targeting microwave hyperthermia sensitizers. Estrogen receptor(ER) is abnormallyexpressed in human breast cancer and has high affinity with estradiol. Free 3-hydroxyl group of estradiol is very important to reserve its affinity with estrogen receptor, so the 17 3 -hydroxyl group is esterified and 3-hydroxyl group is free when crosslinking estradiol and sensitizers. Fifth, verification of the targeting efficacy of thermosensitizers in vivo by measuring the radiation density of implanted human breast cancer in mice after administrating thermosensitizers labelled with 123I, the radiation density of tumor tissue would be different from normal tissue if the thermosensitizers have been targeted to tumor tissue. Finally, the demonstration of thermosensitizing efficacy in vivo is also evaluated in mice xenoimplanted human breast cancer. Tumor growth delay would be investigated after treating with targeting microwave hyperthermia sensitizers and microwave irradiation.Over twenty compounds which absorb microwave energy strongly but little cytotoxicity have been obtained and three compounds(24a-c) which also absorb microwave energy strongly have been synthesized; seven targeting thermosensitizers (I-II-. IV-? V and XII-XIV) and sixteen compounds (2,3,5,7,8, 10,11,12,17,19,33a-c,34a-c) have also been synthesized, all of them have never been reported literaturely. SB^ DHAQ and indolquinone derivatives can increase the temperature faster than control (range from 1.2 °C to 4.3 °C per min) at a power density of 0.18-0.2 mW/cm2 for 2.5min, SB and DHAQ were demonstrated prominently efficacy. The study has desmonstrated it is possible to enhance efficacy of microwave hyperthermia with targeting microwave hyperthermia sensitizers. Because this is a prelimary study of microwave hyperthermia, sequential studies need to be implemented systematically and thoroughly after optimizing experimental conditions.