title: Design, synthesis and cytotoxicity studies of dithiocarbamate ester derivatives of emetine in prostate cancer cell lines.
abstract: A small library of emetine dithiocarbamate ester derivatives were synthesized in 25-86% yield via derivatization of the N2'- position of emetine. Anticancer evaluation of these compounds in androgen receptor positive LNCaP and androgen receptor negative PC3 and DU145 prostate cancer cell lines revealed time dependent and dose-dependent cytotoxicity. With the exception of compound 4c, all the dithiocarbamate ester analogs in this study showed appreciable potency in all the prostate cancer cell lines (regardless of whether it is androgen receptor positive or negative) with a cytotoxicity IC50 value ranging from 1.312 ± 0.032 μM to 5.201 ± 0.125 μM by day 7 of treatment. Compared to the sodium dithiocarbamate salt 1, all the dithiocarbamate ester analogs (2 and 4a-4 g) displayed lower cytotoxicity than compound 1 (PC3, IC50 = 0.087 ± 0.005 μM; DU145, IC50 = 0.079 ± 0.003 μM and LNCaP, IC50 = 0.079 ± 0.003 μM) on day 7 of treatment. Consequently, it appears that S-alkylation of compound 1 leads to a more stable dithiocarbamate ester derivative that resulted in lower anticancer activity in the prostate cancer cell lines.
authors.affiliation: Department of Chemistry, Howard University, 525 College St NW, Washington, DC 20059, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, 1650 Orleans St, Baltimore, MD 21231, USA.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Akinboye
authors.affiliation: Department of Biochemistry and Cancer Center, Howard University, Washington, DC 20059, USA.
authors.forename: Zebalda D
authors.initials: ZD
authors.lastname: Bamji
authors.affiliation: Department of Biochemistry and Cancer Center, Howard University, Washington, DC 20059, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Kwabi-Addo
authors.affiliation: Archer Daniel Midland Company, James R Randall Research Center, Decatur, IL 62521, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ejeh
authors.affiliation: Department of Pharmacology, College of Medicine, Howard University, Adams Bldg., 520 W St NW, Washington, DC 20059, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Copeland
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins School of Medicine, 1650 Orleans St, Baltimore, MD 21231, USA.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Denmeade
authors.affiliation: Department of Chemistry, Howard University, 525 College St NW, Washington, DC 20059, USA. Electronic address: obakare@howard.edu.
authors.forename: Oladapo
authors.initials: O
authors.lastname: Bakare
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015195:Drug Design; D004640:Emetine / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D004640:Emetine
keywords: Anti-cancer activities; Dithiocarbamate ester; Emetine; Emetine derivatives; Prostate cancer