title: Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents.
abstract: To improve the potential of curcumin to treat advanced hormone-refractory prostate cancer, three series (A-C) of heteroaromatic analogs (thirty two compounds) with different monoketone linkers have been synthesized and evaluated for cytotoxicity against two human androgen-independent prostate cancer cell lines (PC-3 and DU-145). Among them, thirty analogs are more potent than curcumin against PC-3 cells, and twenty one analogs are more cytotoxic towards DU-145 cells relative to curcumin. The most potent compounds (44, 45, 51, and 52) also showed impressive cytotoxicity against three other metastatic cancer cell lines (MDA-MB-231, HeLa, and A549), with IC50 values ranging from 50 nM to 390 nM. All four most potent analogs exhibited no apparent cytotoxicity towards the MCF-10A normal mammary epithelial cells. Taken together, selective enhancement of cell death in prostate cancer cell lines and other aggressive cancer cell lines suggests that nitrogen-containing heteroaromatic rings are promising bioisosteres of the substituted phenyl ring in curcumin.
authors: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
authors: Nawras
authors: N
authors: Samaan
authors: Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
authors: Qiu
authors: Q
authors: Zhong
authors: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
authors: Jayjoel
authors: J
authors: Fernandez
authors: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
authors: Guanglin
authors: G
authors: Chen
authors: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
authors: Ali M
authors: AM
authors: Hussain
authors: RCMI Cancer Research Program, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
authors: Shilong
authors: S
authors: Zheng
authors: Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA; RCMI Cancer Research Program, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
authors: Guangdi
authors: G
authors: Wang
authors: Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA. Electronic address: qchen@csufresno.edu.
authors: Qiao-Hong
authors: QH
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Curcumin; Cytotoxicity; Heteroaromatic analogs; Prostate cancer