Synthesis of unsymmetrical biphenyls as potent cytotoxic agents.
Twenty-six unsymmetrical biphenyls were synthesized and evaluated for cytotoxic activity against DU145, A549, KB and KB-Vin tumor cell lines. Three compounds 27, 35 and 40 showed very potent activity against the HTCL panel with an IC(50) value range of 0.04-3.23 microM. In addition, fourteen active compounds were all more potent against the drug-resistant KB-Vin cell line than the parental KB cell line. Preliminary SAR analysis indicated that two bulky substituents on the 2,2'-positions of unsymmetrical biphenyl skeleton are necessary and crucial for in vitro anticancer activity, thus providing a good starting point to develop unsymmetrical biphenyls as novel anticancer agents.
Wu
Gang
G
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Guo
Huan-Fang
HF
Gao
Kun
K
Liu
Yi-Nan
YN
Bastow
Kenneth F
KF
Morris-Natschke
Susan L
SL
Lee
Kuo-Hsiung
KH
Xie
Lan
L
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds
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