Structure-activity relationships of novel heteroaryl-acrylonitriles as cytotoxic and antibacterial agents

European Journal of Medicinal Chemistry
Franciszek SaczewskiPatrick J Bednarski

Abstract

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.

Citations

Nov 4, 2010·Investigational New Drugs·Katja EsterMarijeta Kralj
Oct 12, 2013·European Journal of Medicinal Chemistry·Mohammad Sayed AlamDong-Ung Lee
Oct 23, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pedro de la TorreJorge Trilleras
Mar 11, 2011·Magnetic Resonance in Chemistry : MRC·A Manimekalai, A Balamurugan
Aug 7, 2019·BMC Chemistry·Saloni Kakkar, Balasubramanian Narasimhan
Aug 14, 2018·Chemistry Central Journal·Saloni KakkarBalasubramanian Narasimhan

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