Synthesis and structure-activity relationships of pyridinyl-1H -1,2,3-triazolyldihydroisoxazoles as potent inhibitors of tubulin polymerization

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Suman, Pathi
Murthy, T. Ramalinga
Rajkumar, Kommera
Srikanth, Dudem
Dayakar, Cherupally
Kishor, Chandan
Addlagatta, Anthony
Kalivendi, Shasi V.
Raju, Bhimapaka C.
Griffith University Author(s)
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2015
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Abstract

Three series of compounds; pyridinyl-1H-1,2,3-triazoles, pyridinyl-1H-1,2,3-triazolylisoxazoles and pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles with TMP moiety were designed, synthesized and screened for their anti-cancer and anti-tubulin properties. By sequentially designing three series of compounds comprising of dihydroisoxazole in the linker, a small substituent like chlorine on one side (R1) and aromatic group (R) on the pyridine ring, we have optimized the anti-cancer as well as anti-tubulin activity. Pyridinyl-1H-1,2,3-triazolyldihydroisoxazoles 28b and 28c were found to be potent anti-cancer agents against all the cell lines tested with a concomitant accumulation of cells in the G2/M phase of the cell cycle. Molecular modeling suggests that the trimethoxyphenyl ring in 28b and 28c occupies the cholchicine binding domain of β-tubulin, whereas, the dihydroisoxazole extends towards the interface of α,β-tubulin.

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European Journal of Medicinal Chemistry

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90

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Medicinal and Biomolecular Chemistry not elsewhere classified

Medicinal and Biomolecular Chemistry

Organic Chemistry

Pharmacology and Pharmaceutical Sciences

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