title: Synthesis and antiproliferative activity of some steroidal lactams.
abstract: Using cholesterol as starting material, a series of 6-substituted-3-aza-A-homo-3-oxycholestanes and 6-substituted-4-aza-A-homo-3-oxycholestanes were synthesized by the oxidation, reduction, oximation, Beckman rearrangement and condensation reaction. These synthesized compounds displayed a distinct cytotoxicity against MGC 7901, HeLa and SMMC 7404 cancer cells. Our results revealed that the structures of functional groups at position-6 on the steroidal ring are crucial for the IC(50) value of antiproliferative activities of these compounds and the cytotoxic activity against MGC 7901 and SMMC 7404 cells was not significantly different between 4-N-lactams and 3-N-lactams when its 6-substituted group was a carbonyl or a hydroximino, but all 3-N-lactams showed a higher cytotoxicity against HeLa cells than 4-N-lactams. In particular, compounds 6, 8, 9 (IC(50)6: 6.5 μmol/L; 8: 7.7 μmol/L; 9: 5.6 μmol/L) were even more cytotoxic than cisplatin to HeLa cells (positive contrast, 10.1 μmol/L). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
authors.affiliation: Department of Chemistry, Guangxi Teachers Education University, Nanning 530001, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Huang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cui
authors.forename: Sijing
authors.initials: S
authors.lastname: Chen
authors.forename: Chunfang
authors.initials: C
authors.lastname: Gan
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000031:analogs & derivatives*; D006367:HeLa Cells; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007769:Lactams; D002784:Cholesterol