The scope of thallium nitrate oxidative cyclization of chalcones; synthesis and evaluation of isoflavone and aurone analogs for their inhibitory activity against interleukin-5.
The oxidative cyclization of 2'-hydroxy-6'-cyclohexylmethoxychalcones 5 using thallium (III) nitrate (TTN) in alcoholic solvents produced isoflavones 2 and (or) aurones 3 depending on the electronic nature of p-substituents on ring B. Chalcones with strong electron donating substituents (OH, OCH(3)) were exclusively converted to isoflavones 2. Chalcone with weak electron donating substituents (CH(2)CH(3)) was transformed into isoflavone 2 and the aurone 3 in approximate ratio 1:1. Chalcones with hydrogen or electron withdrawing substituents (Cl, CHO, COOCH(3), and NO(2)) formed aurones 3. Synthesized isoflavones 2 and aurones 3 were evaluated for their inhibitory activity against interleukin-5. Among them, 5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (2h, >100% inhibition at 50 microM, IC(50)=6.1 microM) gave most potent activity. All the aurones 3 were inactive.
Thanigaimalai
P
P
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Yang
Hyun-Mo
HM
Sharma
Vinay Kumar
VK
Kim
Youngsoo
Y
Jung
Sang-Hun
SH
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry*; D003500:Cyclization; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D013793:Thallium / Q000737:chemistry*
C552770:5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one; D001572:Benzofurans; D047188:Chalcones; D015848:Interleukin-5; D007529:Isoflavones; C486837:aurone; D013793:Thallium; C042172:thallium nitrate