N'-Formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide as a potential anti-tumour agent for prostate cancer in experimental studies.
OBJECTIVE
Benzothiazoles (BZTs) represent organic compounds with different biological actions. In this study we aimed to investigate ten newly synthesized BZT derivatives as potential anti-tumour agents against prostate cancer in vitro and in vivo.


METHODS
The cytotoxic effect of these compounds was screened on the human prostate cancer cell lines PC-3 and LNCaP. The most effective compound, N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide, was further characterized regarding its dose- and time-dependent effects on cell viability and proliferation (XTT test) as well as on adhesion and spreading (real-time cell analyzer xCelligence), migration (scratch-wound repair assay) and invasion (Boyden chamber) of the cells. This BZT derivative was also tested as an inhibitor of angiogenesis (chicken chorioallantoic membrane assay), clonogenic activity (soft agar) and matrix metalloproteinase 9 (gelatin zymography).


RESULTS
N'-Formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide significantly inhibited all tested properties of the prostate cancer cell lines and showed low toxic in vitro and in vivo effects. The in vitro anti-tumour activity of this compound was confirmed by the in vivo effects on PC-3 xenografts in nude mice. Tumour growth was decreased in treated compared with untreated mice.


CONCLUSIONS
These results suggest the potential capacity of BZTs and in particular N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide as anti-tumour agents for the treatment of prostate cancer.
Department of Urology, University Hospital Charité, Berlin, Germany.
Juan R
JR
Rodrigues
Jaime
J
Charris
José
J
Camacho
Arthur
A
Barazarte
Neira
N
Gamboa
Bianca
B
Nitzsche
Michael
M
Höpfner
Michael
M
Lein
Klaus
K
Jung
Claudia
C
Abramjuk
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D052160:Benzothiazoles / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014410:Tumor Stem Cell Assay / Q000379:methods; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D006834:Hydrazines; C575386:N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9