Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
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Discovery of ortho-Carborane-Conjugated Triazines as Selective Topoisomerase I/II Inhibitors

Hiroyuki Nakamura A E , Atsushi Shoji A , Ayano Takeuchi A , Hyun Seung Ban A , Jong-Dae Lee B , Takao Yamori C and Sang Ook Kang D
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.

B Department of Chemistry, College of Natural Science, Chosun University, Dong-gu, Kwangju 501-759, South Korea.

C Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550, Japan.

D Department of Chemistry, Korea University, Chochiwon, Chung-nam 339-700, South Korea.

E Corresponding author. Email: hiroyuyki.nakamura@gakushuin.ac.jp

Australian Journal of Chemistry 64(11) 1430-1437 https://doi.org/10.1071/CH11295
Submitted: 16 July 2011  Accepted: 8 August 2011   Published: 16 November 2011

Abstract

The cell growth inhibition profile of 2,4-(2-methyl-ortho-carboranyl)-4-(dimethylamino)-1,3,5-triazine (TAZ-6) was found to be similar to that of ICRF-193, a topoisomerase II inhibitor, as revealed by COMPARE analysis (correlation coefficient (r) = 0.724). Various mono- and di-ortho-carborane-substituted 1,3,5-triazines were synthesized based on the structure of TAZ-6 and tested for their ability to inhibit cell growth and the activities of topoisomerases I and II. Among the compounds synthesized, 3c, 4c, and 4f completely inhibited topoisomerase I activity without affecting topoisomerase II activity, whereas 3a and 3d completely inhibited topoisomerase II activity without affecting topoisomerase I activity, at 100 μM.


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