Parallel synthesis and cytotoxicity evaluation of a polyamine-quinone conjugates library.
A library of 24 derivatives designed by combining two natural products-derived fragments was prepared and tested to determine their anticancer potential in HT29 colon cancer cells. All library members inhibit cell proliferation as measured by MTT mitochondrial functional assay, with IC50 values in the 1-100 microM range. Entry 1b caused apoptotic EGFR-mediated intracellular signaling. Thus, polyamino-quinones emerged as readily accessible and easily diversified scaffolds for anticancer lead discovery.
Bolognesi
Maria Laura
ML
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. marialaura.bolognesi@unibo.it
Calonghi
Natalia
N
Mangano
Chiara
C
Masotti
Lanfranco
L
Melchiorre
Carlo
C
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D011809:Quinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011073:Polyamines; D011809:Quinones; C512478:EGFR protein, human; D066246:ErbB Receptors