Rational design, synthesis, and in vivo evaluation of the antileukemic activity of six new alkylating steroidal esters.
The synthesis and the in vivo evaluation against leukemias P388 and L1210 of six new alkylating steroidal esters are described. The esteric derivatives incorporating the 17beta-acetamido-B-lactamic steroidal skeleton exhibited increased antileukemic activity and lower toxicity, compared to the 17beta-acetamido-7-keto analogs. Among the 17beta-acetamido-B-lactamic steroidal esters, the most potent compound afforded four out of six cures in leukemia P388 and was measured to be almost non-toxic, producing significant low levels of toxicity.
Koutsourea
Anna I
AI
Laboratory of Medicinal Chemistry, School of Health Sciences, Department of Pharmacy, University of Patras, 26500 Rion-Patras, Greece.
Fousteris
Manolis A
MA
Arsenou
Evagelia S
ES
Papageorgiou
Athanasios
A
Pairas
George N
GN
Nikolaropoulos
Sotiris S
SS
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D005260:Female; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013237:Stereoisomerism; D013256:Steroids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004952:Esters; D013256:Steroids