Structure-activity relationships of novel heteroaryl-acrylonitriles as cytotoxic and antibacterial agents.
Eighteen new 2,6-disubstituted acrylonitriles and two new (benzimidazol-1-yl)-acetamide derivatives were prepared and screened for antibacterial and cytotoxic activities on 12 human cancer cell lines. Based on the lead structure 2-(benzimidazol-2-yl)-3-(5-nitrothiophen-2-yl) acrylonitrile it was found that placement of methyl groups at the 5,6 positions of the benzimidazole ring lead to a 3-fold increase in overall cytotoxic activity. Replacing the nitrothiophene for pyridine reduced cytotoxic activity as did replacing the nitro group for a methoxy group. Cytotoxic activity was only slightly reduced when the benzimidazole ring was replaced by a imidazo[4,5-b]pyridine or a benzthiazole ring but replacement by benzoxazole led to a substantial decrease in activity. Moving the acrylonitrile group from position 2 to position 1 of the benzimidazole ring also resulted in moderately active compounds. (Benzimidazol-1-yl)acetamides showed only modest activity. The structure-activity relationships found in the cytotoxicity studies are mirrored in the results of the antibacterial experiments.
Saczewski
Franciszek
F
Department of Chemical Technology of Drugs, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland. saczew@amg.gda.pl
Stencel
Agnieszka
A
Bieńczak
Andrzej M
AM
Langowska
Karolina A
KA
Michaelis
Martin
M
Werel
Władysław
W
Hałasa
Rafał
R
Reszka
Przemyslaw
P
Bednarski
Patrick J
PJ
D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D011725:Pyridines / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011725:Pyridines; D000181:Acrylonitrile; C023666:pyridine