Synthesis and antitubercular activity of quaternized promazine and promethazine derivatives.

نویسندگان

  • Aaron B Bate
  • Jay H Kalin
  • Eric M Fooksman
  • Erica L Amorose
  • Cristofer M Price
  • Heather M Williams
  • Michael J Rodig
  • Miguel O Mitchell
  • Sang Hyun Cho
  • Yuehong Wang
  • Scott G Franzblau
چکیده

Quaternized chlorpromazine, triflupromazine, and promethazine derivatives were synthesized and examined as antitubercular agents against both actively growing and non-replicating Mycobacterium tuberculosis H37Rv. Impressively, several compounds inhibited non-replicating M. tuberculosis at concentrations equal to or double their MICs against the actively growing strain. All active compounds were non-toxic toward Vero cells (IC50 > 128 microM). N-Allylchlorpromazinium bromide was only weakly antitubercular, but replacing allyl with benzyl or substituted benzyl improved potency. An electron-withdrawing substituent on the phenothiazine ring was also essential. Branching at the carbon chain decreased antitubercular activity. The optimum antitubercular structures possessed N-(4- or 3-chlorobenzyl) substitution on triflupromazine.

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عنوان ژورنال:
  • Bioorganic & medicinal chemistry letters

دوره 17 5  شماره 

صفحات  -

تاریخ انتشار 2007