Study on anti-proliferative effect of benzoxathiole derivatives through inactivation of NF-κB in human cancer cells.
To investigate the anti-proliferative effect of a newly discovered NF-kB inhibitor, 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one (1a), a series of its analogs (1b-n) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Slight variation of hydrophobicity by replacement of dimethyl group of 1a at 6-position with bulky isopropyl group and introduction of para-fluoro substitution on 2-phenyl group showed good NF-κB inhibitory activity and anti-proliferative activity. However, excessive increase in hydrophobicity with 2,4,6-trichloro substituents on phenyl group resulted in the loss of both the activities. From the SAR results, 2-phenylimino-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one was identified as the lead scaffold for investigating new anticancer agent through inactivation of NF-κB.
College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Eeda
E
Venkateswararao
Hoang Le Tuan
Hle T
Anh
Vinay K
VK
Sharma
Ki-Cheul
KC
Lee
Niti
N
Sharma
Youngsoo
Y
Kim
Sang-Hun
SH
Jung
D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000494:pharmacology
D001555:Benzene Derivatives; D016328:NF-kappa B; D013438:Sulfhydryl Compounds