Antitumor and cytogenetic effects of esteric (ASE) and amidic (ASA) steroidal derivative of p-bis (2-chloroethyl) amino phenylacetic acid (CAPA). A comparative study.
The homo-aza-steroidal ester of p-bis (2-chloroethyl) amino phenylacetic acid (ASE) (I) the homo-aza-steroidal amide of p-bis (2-chloroethyl) amino phenylacetic acid (ASA) (II), and the parent compound p-bis (2-chloroethyl) amino phenylacetic acid (III) were tested in an effort to evaluate their ability to inhibit a transplanted leukemia (P388) in vivo, and the DNA synthesis of P388 cell cultures in vitro. The compounds' effects on Sister Chromatid Exchange (SCE) rate and on human cell proliferation kinetics in vitro were also studied. The above mentioned compounds were identified as displaying cytogenetic, cytostatic and antineoplastic effects, the ester compound being the more potent. The main conclusion from this study is that the existence of the esteric bond is necessary for the expression of the antitumor activity. The synthetic route for the preparation of the amidic derivative (II), as new product, is also reported.
Nikolaropoulos
S S
SS
School of Health Sciences, Department of Pharmacy, University of Patras, Greece. snikolar@upatras.gr
Arsenou
E S
ES
Papageorgiou
A
A
Mourelatos
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007928:Lethal Dose 50; D007941:Leukemia P388 / Q000188:drug therapy*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009153:Mutagens / Q000633:toxicity*; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013256:Steroids / Q000627:therapeutic use / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D013256:Steroids; C008826:phenacid