Anti-cancer activities of 1,4-naphthoquinones: a QSAR study.
Quinone moieties are present in many drugs such as anthracyclines, daunorubicin, doxorubicin, mitomycin, mitoxantrones and saintopin, which are used clinically in the therapy of solid cancers. The cytotoxic effects of these quinones are mainly due to the following two factors: (i) inhibition of DNA topoisomerase-II and, (ii) formation of semiquinone radical that can transfer an electron to oxygen to produce super oxide, which is catalyzed by flavoenzymes such as NADPH-cytochrome-P-450 reductase. Both semiquinone and super oxide of quinones can generate the hydroxyl radical, which is the cause of DNA strand breaks. 1,4-naphthoquinone contains two quinone groups that have the ability to accept one or two electrons to form the corresponding radical anion or di-anion species. It is probably dependent on the quinone redox cycling that yields "reactive oxygen species" (ROS) as well as arylation reactions, which is common to quinones for biological relevance. In the present review, an attempt has been made to collect the cytotoxicity data on different series of 1,4-naphthoquinones against four different cancer cell lines that are L1210, A549, SNU-1, and K562, which were acquired by using identical method, and has been discussed in terms of QSAR (quantitative structure-activity relationships) to understand the chemical-biological interactions. QSAR results have shown that the cytotoxic activities of 1,4-naphthoquinones depend largely on their hydrophobicity.
Verma
Rajeshwar P
RP
Department of Chemistry, Pomona College, Claremont, CA 91711, USA. rverma@pomona.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020014:K562 Cells / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy; D008942:Mitoxantrone / Q000627:therapeutic use; D009285:Naphthoquinones / Q000627:therapeutic use*; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D004317:Doxorubicin; D008942:Mitoxantrone; C035342:1,4-naphthoquinone