INVITRO CYTOTOXICITY AND DIFFERENTIAL CELLULAR-SENSITIVITY OF NEW N-METHYL AND N-PROPARGYL UREA AND NITROSOUREA DERIVATIVES OF DIAMINO ACIDS AGAINST 60 HUMAN NCI TUMOR-CELL LINES

The in vitro cytotoxicity and differential cellular sensitivity of a s eries of new N-methyl and N-propargyl urea and nitrosourea derivatives of diamino acids were determined in the National Cancer Institute's p rimary antitumor drug screen. These compounds have a level of cytotoxi c activity comparable to BCNU, CCNU and Methyl-CCNU. In this series of diamino acid derivatives, the N-nitroso group does not seems to be es sential to the in vitro activity of these compounds. The N-Propargyl d erivatives have shown significantly more differential cellular sensiti vity than the N-Methyl derivatives. Hence, the N-Propargyl group seems to induce more cell line specificity in our compounds. Based on their in vitro cytotoxic activity and mostly their pattern of differential cellular sensitivity, two compounds described in this work have been s elected by the NCI for further development. These compounds are curren tly being screened in animal models.