Synthesis and structure-activity relationship studies of cytotoxic anhydrovinblastine amide derivatives.
A series of 3-demethoxycarbonyl-3-amide methyl anhydrovinblastine derivatives (5b-24b) was designed, synthesized, and evaluated for their proliferation inhibition activities against two tumor cell lines (A549 and HeLa). Most of the amide anhydrovinblastine derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic activity. Test results in vivo against sarcoma 180 of three potent compounds (6b, 12b, and 24b) indicated that the introduction of an amide group at the 22-position of anhydrovinblastine (1e) improved both potency and toxicity.
Shao
Yong
Y
Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Zhang
Han-Kun
HK
Ding
Hong
H
Quan
Hai-Tian
HT
Lou
Li-Guang
LG
Hu
Li-Hong
LH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D000077235:Vinorelbine