title: Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line.
abstract: In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one and evaluated against the androgen-sensitive human prostate adenocarcinoma LNCaP cell line. The cancerous cells were exposed to 50 μM of each compound and the proliferating agent testosterone (T) or dihydrotestosterone (DHT). The most potent compounds from this assay were further tested against the androgen-insensitive PC3 cell line. We also demonstrate the activity of these compounds on rat peripheral blood mononuclear cells for comparison. Both 17β-N-[3,5-bis(trifluoromethyl)phenylcarbamoyl]androst-4-ene-3-one (6f) and 17β-N-(1,3-thiazol-2-ylcarbamoyl)androst-4-ene-3-one (6g) exhibited a higher growth inhibitory effect than commercially available drugs finasteride, flutamide and ketoconazole on LNCaP cells in the presence and absence of androgens. In addition, 6f and 6g demonstrated high potency on PC3 cells suggesting an androgen-independent anti-proliferative effect. Moreover, the novel compounds showed a small effect on rat mononuclear cells, an indication of low toxicity.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D. F., 04510, Mexico. Electronic address: franciscoqfb@comunidad.unam.mx.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cortés-Benítez
authors.affiliation: Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, México, D. F., 04960, Mexico. Electronic address: marisa@correo.xoc.uam.mx.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
authors.affiliation: Unidad de Pruebas Biológicas, Instituto de Química, Universidad Nacional Autónoma de México, México, D. F., 04510, Mexico. Electronic address: mtrapan@unam.mx.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Ramírez-Apan
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D. F., 04510, Mexico. Electronic address: alvarez.m.berenice@gmail.com.
authors.forename: Berenice
authors.initials: B
authors.lastname: Alvarez-Manrique
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, México, D. F., 04510, Mexico.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000736:Androstenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D051381:Rats
chemical_list: D000728:Androgens; D000736:Androstenes; D000970:Antineoplastic Agents
keywords: Androst-4-en-3-one derivatives; LNCaP cells; PC3 cells; Prostate cancer; Rat peripheral blood mononuclear cells (PBMC); Sulforhodamine B assay