title: Hybrid anticancer compounds. Steroidal lactam esters of carboxylic derivatives of N,N-bis (2-chloroethyl) aniline (review).
abstract: For the rational design of more specific alkylating agents, we suggested new biological platforms able to deliver the alkylating moieties to specific target site and on the other hand we hoped to lead in compounds with synergistic activity. As biological platforms have been used steroidal lactams of A and D- ring and as alkylating agents carboxylic derivatives of N,N-bis (2-Chloroethyl) aniline which combine to the steroid by an easily cleaved ester bond. These homo-aza-steroidal esters gave satisfactory results in early and advanced P388, L1210 leukemias and solid tumors. Whereas unmodified steroidal esters have generally been reported to be inactive in treatment of L1210 leukemia. The steric arrangement of the alkylating moiety greatly effects toxicity and activity of the drugs, while the steric arrangement of the hydrogen atom at position 5 influences these parameters. Isosterism of alkylating agent is the factor for biological action. The amide group of the lactam molecule may be essential for activity.
authors.affiliation: School of Health and Sciences, Department of Pharmacy, University of Patras, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Catsoulacos
authors.forename: D
authors.initials: D
authors.lastname: Catsoulacos
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry / Q000494:pharmacology*; D000816:Aniline Mustard / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D007769:Lactams / Q000737:chemistry / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000477:Alkylating Agents; D000970:Antineoplastic Agents; D007769:Lactams; D000816:Aniline Mustard