title: Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics.
abstract: Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.
authors.affiliation: Laboratory of Pharmacology, Medical School National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece. Electronic address: dtrafal@med.uoa.gr.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trafalis
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
authors.forename: Elena
authors.initials: E
authors.lastname: Geromichalou
authors.affiliation: Laboratory of Pharmacology, Medical School National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Dalezis
authors.affiliation: Laboratory of Pharmacology, Medical School National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Nikoleousakos
authors.affiliation: Department of Chemistry, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece. Electronic address: sarli@chem.auth.gr.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Sarli
mesh_terms: D000816:Aniline Mustard / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007941:Leukemia P388 / Q000188:drug therapy*; D008297:Male; D008466:Mechlorethamine / Q000737:chemistry; D008807:Mice, Inbred BALB C; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007769:Lactams; D013256:Steroids; D008466:Mechlorethamine; D000816:Aniline Mustard
keywords: Alkylating agent; Antileukemic agent; Homo-aza-steroidal alkylators; Nitrogen mustard; Steroidal lactam