Design and synthesis of new mitochondrial cytotoxin N-thiadiazolylanilines that inhibit tumor cell growth.
New N-thiadiazolylanilines were designed and synthesized to develop mitochondrial cytotoxins superior to SF 6847. The mitochondrial cytotoxin N-thiadiazolylanilines, TX-108 and TX-109, inhibited EMT6/KU mammary sarcoma cell growth at a low micromolar concentration. Their inhibitory activities were parallel to their mitochondrial cytotoxicity, such as uncoupling oxidative phosphorylation and inhibiting ATP synthesis. This report also supports the notion that the inhibition of tumor cell growth of inhibitor of protein tyrosine kinase AG17, which is identical to SF 6847, may be due to its mitochondrial cytotoxicity.
Hori
H
H
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Japan, hori@bio.tokushima.u.ac.jp
Noguchi
N
N
Yokoyama
H
H
Ise
H
H
Jin
C Z
CZ
Kasai
S
S
Goto
T
T
Taira
Z
Z
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000473:pathology*; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents / Q000494:pharmacology
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D003603:Cytotoxins; D009570:Nitriles; C101192:TX 108; C101193:TX 109; D013830:Thiadiazoles; D014475:Uncoupling Agents; C001784:SF 6847; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases