Synthesis and structure-activity relationships of 2-amino-1-aroylnaphthalene and 2-hydroxy-1-aroylnaphthalenes as potent antitubulin agents.
A series of aroylnaphthalene derivatives were prepared as bioisosteres of combrestatin A-4 and evaluated for anticancer activity. 2-Amino-1-aroylnaphthalene and 2-hydroxy-1-aroylnaphthalene, 9 and 8, respectively, showed strong antiproliferative activity with IC(50) values of 2.1-26.3 nM against a panel of human cancer cell lines including multiple-drug resistant cell line. Compound 9 demonstrated better antiproliferative activity and has a comparable tubulin binding efficacy as that of colchicine.
Reddy
Gadarla Randheer
GR
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
Kuo
Ching-Chuan
CC
Tan
Uan-Kang
UK
Coumar
Mohane Selvaraj
MS
Chang
Chi-Yen
CY
Chiang
Yi-Kun
YK
Lai
Mei-Jung
MJ
Yeh
Jiann-Yih
JY
Wu
Su-Ying
SY
Chang
Jang-Yang
JY
Liou
Jing-Ping
JP
Hsieh
Hsing-Pang
HP
D000840:Anisoles / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
D000840:Anisoles; D007211:Indoles; D009281:Naphthalenes; D014404:Tubulin; D050257:Tubulin Modulators; C031721:naphthalene