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Synthesis and pharmacological studies of new pyrazole analogues of podophyllotoxin

Abstract

The pyrazole analogues of podophyllotoxin were synthesized by the chalcone route. This route attracts the attention because of its simple operating conditions and easy availability of the chemicals. Initially, benzylideneacetophenones (chalcones) were prepared in high yields by Claisen-Schmidt reaction of acetophenones with 4-(methylthio)benzaldehyde. The cyclopropyl ketones were prepared in good yields by the reaction of chalcones with trimethylsulfoxonium iodide. Tetralones were prepared in good yields by the Friedel-Craft’s intramolecular cyclization reaction of cyclopropyle ketones in the presence of anhyd. stannic chloride and acetic anhydride. The tetralones on formylation to give substituted hydroxylmethylene tetralones. Condensation of substituted hydroxylmethylene tetralones with hydrazine hydrate afforded target compounds. The structures of the synthesized compounds were confirmed by IR, 1H NMR and Mass spectral technique. The title compounds were screened for their antimitotic and antimicrobial activities. Among the synthesized compounds cyclopropyl ketones and pyrazole analogues of podophyllotoxin, compound 7-(methylthio)-5-(4-(methylthio)phenyl)-4,5-dihydro-2 H-benzo[g]indazole is more active than 5-(4-(methylthio)phenyl)-4,5-dihydro-2 H-benzo[g]indazole, 7-methyl-5-(4-(methylthio)phenyl)-4,5-dihydro-2 H-benzo[g]indazole, 7-methoxy-5-(4-(methylthio)phenyl)-4,5-dihydro-2 H-benzo[g]indazole and the key intermediate tetralones in 100, 200 and 400 ppm at 12, 18 and 24 h and also showed very good activity against screened bacteria and fungi compared to their standard.

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Correspondence to Y. B. Basavaraju.

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Umesha, B., Basavaraju, Y.B. Synthesis and pharmacological studies of new pyrazole analogues of podophyllotoxin. Russ J Bioorg Chem 40, 467–476 (2014). https://doi.org/10.1134/S106816201404013X

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  • DOI: https://doi.org/10.1134/S106816201404013X

Keywords

  • acetophenones
  • chalcones
  • cyclopropylketones
  • tetralones
  • antimitotic activity
  • antimicrobial activity