ADDUCTS OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE 5'-PHOSPHATE OR 5'-HYDROGENPHOSPHONATE AS INHIBITORS OF RETROVIRAL CYTOPATHICITY AND CELL-TRANSFORMATION IN CULTURE

Adducts of some amino alcohols and amino acids with 3'-azido-2',3'-did eoxythymidine 5'-phosphate (AZTMP) or its 5'-hydrogenphosphonate (AZTH P) have been obtained and assayed for their effect on the cytopathicit y of human immunodeficiency virus (HIV-1 and HIV-2) and on cell transf ormation by (Moloney) murine sarcoma virus (MSV) in cell culture. Both groups of compounds were shown to be 1.5-3 times weaker than 3'-azido -2',3'-dideoxythymidine (AZT) in suppressing the cytopathic effect of HIV-1 and HIV-2 in MT-4 cells. The toxicity of AZTMP for the cells was 1.5-2 times higher than that of AZT, while AZTHP was somewhat less to xic than AZT. The selectivity index for all compounds was 1.5-3 times lower than that of AZT. At the same time, AZTMP adducts suppressed MSV in C3H/3T3 cells approximately to the same extent as AZT but were 2 t o 10 times less toxic, so that their selectivity index increased up to 7-fold. Adducts of AZTHP were 2-3 times weaker than AZT in blocking M SV -induced cell transformation but were at least 10 times less toxic, and their selectivity index was 7 times higher. The nature of the ami no acid did not appreciably influence the activity of any compound. Th e probable causes of the observed phenomena are discussed.