title: An overview on the antileukemic potential of D-homo-aza- and respective 17beta-acetamido-steroidal alkylating esters.
abstract: In order to reduce toxicity and to increase antineoplastic activity, steroid molecules were utilized as biological vectors for chemotherapeutic agents. Several modified steroid compounds as 17beta-acetamido and D-homo-aza steroids that contain the NHCO group outside or inside D steroid ring, respectively, were used in the synthesis of steroidal esters carrying alkylating moieties. As it has been reported previously, several of these compounds produced important both antileukemic and antitumor results. In this work, we comparatively study, evaluate, and conclude on the acute toxicity on mice, the in vivo antileukemic activity against P388 and L1210 murine leukemias, as well the in vitro antileukemic effect on three well established human leukemia cell lines (K562, MOLT-4, ML-1) of eight D-homo-aza-steroidal (HASE) and the corresponding steroidal 17beta-amido-esters (SAE) of three alkylating molecules. The compound screening indicated that HASE induced lower acute toxicity and significant higher antileukemic effect than SAE, both in vivo and in vitro. Furthermore, the structure of the homo-aza-steroidal vector seems to be a determinant of the toxicity and antineoplastic activity of the esters. Conclusively, HASE presented low acute toxicity but significant high antileukemic activity. These results point out that HASE may be of important therapeutic efficacy in the treatment of leukemia in humans.
authors.affiliation: Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, Faculty of Pharmacy, School of Health Science, University of Patras, Greece. c.kamoutsis@upatras.gr
authors.forename: Charalambos
authors.initials: C
authors.lastname: Camoutsis
authors.forename: Dimitrios T P
authors.initials: DT
authors.lastname: Trafalis
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000627:therapeutic use* / Q000633:toxicity; D001378:Azasteroids / Q000138:chemical synthesis / Q000627:therapeutic use* / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D007942:Leukemia, Experimental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D015996:Survival Rate
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001378:Azasteroids; D004952:Esters