title: Conjugated system of homo-aza-steroidal esters in cancer chemotherapy.
abstract: The homo-aza-steroidal esters of conjugated carboxylic derivatives of nitrogen mustards are reviewed. Particularly we discuss the antitumor activity of cinnamic acid and benzoic acid mustard isomers, esters of homo-aza-steroids in which the mustard acid is linked to the C-3 or C17 position, while the lactam nucleus is in the D or A ring of the steroid respectively. The current literature indicates that the potential is due to the synergistic activity of both the steroidal lactam and the mustard of the acids. Steroidal lactams, namely 3 beta-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17-lactam, the isomer 3 alpha-hydroxy-13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic- 13,17-lactam, 3 beta-hydroxy-13 alpha-amino 13,17-seco-5-androsten-17-oic-13,17-lactam and the 17 beta-hydroxy-3-aza-A-homo- 4 alpha-androsten-4-one, have been used as biological platforms of the cinnamic acid, of the benzoic acid mustard isomers and the 4-methyl-benzoic acid mustard. The twelve esters of cinnamic acid mustard isomers were tested against P388, L1210 leukemias Ehrlich ascites tumor (EAT) and melanoma B16 in vivo. The effect of homo-aza-steroidal esters of N,N-bis(2-chloroethyl) amino cinnamic acid isomers on the incorporation of the radioactive precursors into DNA, RNA and proteins of L1210, P388 leukemias, Ehrlich ascites tumor (EAT) and Baby Hamster Kidney (BHK) cells, was investigated. The effect of the homo-aza-steroidal esters of N,N-bis(2-chloroethyl) aminobenzoic acid isomers on the incorporation of radioactive precursors into DNA, RNA and proteins was studied in L1210, P388 leukemias, Ehrlich ascites tumor and Baby hamster kidney cells.
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: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D001378:Azasteroids / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D006718:Homosteroids / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D007668:Kidney; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000187:drug effects; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001378:Azasteroids; D004273:DNA, Neoplasm; D006718:Homosteroids; D009363:Neoplasm Proteins; D009588:Nitrogen Mustard Compounds; D012334:RNA, Neoplasm