Synthesis and Evaluation of Nicotinoylamino Acid Compounds as Radiosensitizer

Nicotinoylamino acid compounds 4, 5, 9a, 9b, 9c, 10a and 10b were synthesized with nicotinoyl chloride or nicotinoyl azide as acetylating agents of amino acid esters or amino acids. The compounds were tested for their radiosensitizing activity in Leukemia cell line(L1210) and compared with nicotinamide; among them, compounds 9a and 9c showed significant radiosensitizing effects, the sensitizer enhancement ratio(SER) was 1.64 and 1.58, respectively, while nicotinamide did not show good radiosensitizing effect under the same conditions. Compound 9c was alone tested for radiosensitization in LA 795 cell-bearing T-739 mice, or hyperthermia and breathing carbogen(5%CO2+95%O2) were together tested for radiosensitization. The results showed that radiation-induced growth delay was enhanced by 9c alone or by the combination of hypertheimia and carbogen. The tumor-bearing mice were irradiated locally by total 10 Gy, and the tumors grew to three times that of the original volume in an average of 5.8 d. The mice were given i.p. compound 9c at 1000 mg/kg 60 min before irradiation and treated at 43 °C for 30 min after irradiation or treated with breathing carbogen for 5 min before radiation or with hyperthmia(43 °C) for 30 min after irradiation; the time required for the tumor to grow to three times the orginal volume was in an average of 12.9 and 13 d, respectively.