Novel heterocyclic family of phenyl naphthothiazole carboxamides derived from naphthalimides: synthesis, antitumor evaluation, and DNA photocleavage.
A new heterocyclic family of (2-(dimethylamino)ethyl)-2-substituted phenylnaphtho[2,1-d]thiazole-5-carboxamides modified from naphthalimides was designed, synthesized, and quantitatively evaluated as antitumor agents and photonucleases. All these compounds were found to be more cytotoxic against P388 than against A549. B(3) (m-NO(2)) was found to be the strongest inhibitor for P388 with IC(50) of 1.49 microM, while B(2) was the most cytotoxic compound against A549 with IC(50) of 12 microM. B(4) (p-CH(3)), the most efficient DNA photocleaver, showed detectable DNA cleavage at 0.5 microM and total cleavage from form I to 100% form II at 50 microM. The photocleaving mechanism was changed with the modification to be via superoxide anion and radical.
Li
Zhigang
Z
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China.
Yang
Qing
Q
Qian
Xuhong
X
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010782:Photolysis; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D007094:Imides; D017319:Photosensitizing Agents; D004247:DNA