Details

Autor(en) / Beteiligte

• Papaconstantinou, Ioanna C
• Fousteris, Manolis A
• Koutsourea, Anna I
• Pairas, Georgios N
• Papageorgiou, Athanasios D
• Nikolaropoulos, Sotiris S

Titel

Steroidal esters of the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl)amino-phenyl]butanoic acid (2-PHE-BU): synthesis and in-vivo biological evaluation

Ist Teil von

• Anti-cancer drugs, 2013-01, Vol.24 (1), p.52-65

Ort / Verlag

England: Lippincott Williams & Wilkins, Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• On the basis of the results of in-silico predictions and in an effort to extend our structure–activity relationship studies, the aromatic nitrogen mustard 2-[4-N,N-bis(2-chloroethyl) amino-phenyl]butanoic acid (2-PHE-BU) was synthesized and conjugated with various steroidal alcohols. The resulting steroidal esters were evaluated for their in-vivo toxicity and antileukemic activity in P388-leukemia-bearing mice. The new derivatives showed significantly reduced toxicity and marginally improved antileukemic activity compared with free 2-PHE-BU. Nevertheless, they did not prove to be superior either to the template steroidal ester used for in-silico predictions or to previously synthesized steroidal esters of aromatic nitrogen mustards. The results obtained indicate that in-silico design predictions may guide the design and synthesis of new bioactive steroidal esters, but further parameters should be considered aiming at the discovery of compounds with optimum activity.