Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.
A series of novel antitumor and DNA photocleaving agents was designed and synthesized by fusing a (substituted) thiazole ring to the naphthalimide skeletons. C1, the most active compound against A549, was about 30-fold more cytotoxic than the compound amonafide. A1, the most active compound against P388, was about 6-fold more cytotoxic than amonafide. C2, the most efficient DNA intercalator, showed the strongest DNA photocleaving activity via superoxide anion produced under UV light at 360 nm.
Li
Zhigang
Z
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China.
Yang
Qing
Q
Qian
Xuhong
X
D000225:Adenine; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007094:Imides / Q000737:chemistry / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053644:Naphthalimides; D063065:Organophosphonates; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D007094:Imides; D007364:Intercalating Agents; D007546:Isoquinolines; D009281:Naphthalenes; D053644:Naphthalimides; D063065:Organophosphonates; D010797:Phthalimides; D013829:Thiadiazines; C037020:amonafide; C031721:naphthalene; D004247:DNA; C427203:calf thymus DNA; D000225:Adenine