title: Synthesis and cytotoxic effect on cancer cell lines and macrophages of novel progesterone derivatives having an ester or a carbamate function at C-3 and C-17.
abstract: In this study we report the cytotoxic effect on human cancer cells of two series of novel progesterone derivatives; the first containing an aromatic ester (8a-e) or a carbamate functions both linked to C-3 (9a-e) on the pregn-4,16-diene-6,20-dione skeleton. In the second series, both functional groups (ester and carbamate) are bound to C-17 on the pregn-4,6-diene-3,20-dione scaffold (13a-e and 14a-e). The panel cancer cell lines used in this study were the following: PC-3 (human prostate cancer cell line), MCF-7 (human breast cancer cell line), HCT-15 (human colon cancer cell line) and J774 (noncancerous murine macrophages) for comparison. The results from this study showed that steroid 14a, having a carbamate function at C-17, was the most potent against PC-3 cell line (96.6%) while 8c and 8e showed much higher cytotoxic activity (100%) for MCF-7 cell line. Finally, compounds 8c and 14a displayed selective properties towards tumor cell lines than noncancerous murine macrophages.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico. Electronic address: alechavezriveros@hotmail.com.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Chávez-Riveros
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
authors.forename: Mariana
authors.initials: M
authors.lastname: Garrido
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, DF 04510 D.F., Mexico.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ramírez Apan
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Zambrano
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, D.F. 04510, Mexico.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D011374:Progesterone / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D004952:Esters; D011374:Progesterone
keywords: Carbamates; Cytotoxic effect; Esters; Progesterone derivatives; Synthesis