Antitumor activity of homo-aza-steroidal esters of [p-[bis(2-chloroethyl)amino]phenyl]acetic acid and [p-[bis(2-chloroethyl)amino]phenyl]butyric acid |
| |
Authors: | Panayotis Catsoulacos Dimitrios Politis Galen L. Wampler |
| |
Affiliation: | (1) University of Patras, Patras, Greece;(2) Division of Medical Oncology, Virginia Commonwealth University, Box 230, 23298 Richmond, VA, USA |
| |
Abstract: | Summary Three new modified steroidal alkylating agents, 3 -hydroxy-13 -amino-13,17-seco-5 -androstan-17-oic-13,17-lactam-p-bis(2-chloroethyl)aminophenylacetate, 3 -hydroxy-13 -amino-13,17-seco-5 -androstan-17-oic-13,17-lactam-p-bis-(2-chloroethyl)aminophenylbutyrate, and 17 -hydroxy-3-aza-A-homo-4 -androsten-4-one-p-N,N-bis(2-chloroethyl)-aminophenylacetate are active in treatment of L1210 and P388 leukemias. A stereoisomer of the first compound, 3 -hydroxy-13 -amino-13,17-seco-5 -androstan-17-oic-13, 17-lactam-p-bis(2-chloroethyl)aminophenylacetate, was tested in L1210 leukemia. This stereoisomer, in which the alkylating agent is linked to the modified steroid in the axial position, is active only at much higher doses in L1210 leukemia. The results of testing these compounds and previous results from similar compounds allow certain conclusions to be drawn regarding structure-activity relationships. The presence of the lactam moiety is the major structural feature that confers activity in the murine leukemias. The steric arrangement of the alkylating moiety at position 3 and the hydrogen atom at position 5 influence toxicity and antileukemic activity. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|