A laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity.
Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a co-solvent, dimethylformamide, under mild reaction conditions in a vessel open to air at pH 4.5 and pH 6.0. Anticancer screening showed that the aminonaphthoquinones exhibited potent cytostatic effects particularly against the UACC62 (melanoma) cancer cell line (GI(50)=3.98-7.54 μM). One compound exhibited potent cytostatic effects against both the TK10 (renal) and the UACC62 (melanoma) cancer cell line. The cytostatic effects of this compound (GI(50)=8.38 μM) against the TK10 cell line was almost as good as that of the anticancer agent, etoposide (GI(50)=7.19μM). Two compounds exhibited potent cytostatic effects against both the UACC62 (melanoma) and the MCF7 (breast) cancer cell lines. The total growth inhibition (TGI) of most of the compounds was better than that of etoposide against the UACC62 cell line. Three compounds (TGI=7.17-7.94 μM) exhibited potent cytostatic effects against the UACC62 cell line which was 7 to 8-fold better than that of etoposide (TGI=52.71 μM). The results are encouraging for further study of the aminonaphthoquinones for potential application in anticancer therapy.
CSIR Biosciences, PO Box 395, Pretoria, South Africa. kwellington@csir.co.za
Kevin W
KW
Wellington
Natasha I
NI
Kolesnikova
D000588:Amines / Q000737:chemistry; D055162:Biocatalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D042845:Laccase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013696:Temperature
D000588:Amines; D054697:Cytostatic Agents; D006873:Hydroquinones; C063601:1,4-naphthohydroquinone; D042845:Laccase