19044-89-4Relevant academic research and scientific papers
Synthesis and Antitubulin Activity of N1- and N 4-Substituted 3,5-Dinitro Sulfanilamides against African Trypanosomes and Leishmania
Bhattacharya, Gautam,Herman, Johnathan,Delfín, Dawn,Salem, Manar M.,Barszcz, Todd,Mollet, Mike,Riccio, Guy,Brun, Reto,Werbovetz, Karl A.
, p. 1823 - 1832 (2004)
Thirty analogues of N1-phenyl-3,5-dinitro-N4,N 4-di-n-propylsulfanilamide (GB-II-5, compound 3), a new antikinetoplastid antimitotic agent, have been synthesized and evaluated. The addition of simple functional groups to the N1 aromatic ring generally decreases antiparasitic and antimitotic potency, but placement of a dibutyl substituent at the N4 nitrogen to give N1-phenyl-3,5-dinitro-N 4,N4-di-n-butylsulfanilamide (compound 35) augments antitrypanosomal and antileishmanial activity. Compound 35 possesses IC 50 values of 0.12 and 2.6 μM against cultured T. brucei and L. donovani amastigote-like forms, surpassing the activity of compound 3 against these parasites by 3.4- and 1.9-fold, respectively. Compound 35 inhibits the assembly of leishmanial tubulin with an IC50 of 6.9 μM and displays antimitotic effects in cultured T. brucei as assessed by flow cytometry, but shows little effect on purified mammalian tubulin, and displays 100-fold selectivity for trypanosomes over two mammalian cell lines. Although 3 and 35 were not effective in initial in vivo antitrypanosomal assays, the in vitro potency and selectivity of these compounds make N 1-aryl-3,5-dinitro-N4,N4-dialkylsulfanilamides a promising new class of antikinetoplastid agents that act on parasite tubulin.
