Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.
In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Significantly, these derivatives exhibited comparable cytotoxicity against KBvin, while irinotecan was less active against this cell line. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, these compounds merit further development as a new generation of CPT-derived PEG-conjugated drug candidates.
['Song|Zi-Long|ZL|', 'Chen|Hai-Le|HL|', 'Wang|Yu-Han|YH|', 'Goto|Masuo|M|', 'Gao|Wen-Jing|WJ|', 'Cheng|Pi-Le|PL|', 'Morris-Natschke|Susan L|SL|', 'Liu|Ying-Qian|YQ|', 'Zhu|Gao-Xiang|GX|', 'Wang|Mei-Juan|MJ|', 'Lee|Kuo-Hsiung|KH|']
D000970:Antineoplastic Agents D002166:Camptothecin D002384:Catalysis D045744:Cell Line, Tumor D049109:Cell Proliferation D003300:Copper D015195:Drug Design D004354:Drug Screening Assays, Antitumor D006801:Humans D000077146:Irinotecan D007624:KB Cells D011092:Polyethylene Glycols D013329:Structure-Activity Relationship
Sulfonylamidine Camptothecin Cytotoxic activity C-20 position Poly(ethylene glycol) (PEG)