000151178 001__ 151178
000151178 005__ 20181203021956.0
000151178 022__ $$a1464-3391
000151178 02470 $$2PMID$$a20133138
000151178 02470 $$2ISI$$a000274425500012
000151178 0247_ $$2doi$$a10.1016/j.bmc.2010.01.013
000151178 037__ $$aARTICLE
000151178 245__ $$aAntimalarial and antitubercular nostocarboline and eudistomin derivatives: synthesis, in vitro and in vivo biological evaluation
000151178 269__ $$a2010
000151178 260__ $$c2010
000151178 336__ $$aJournal Articles
000151178 520__ $$aThe synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-Cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin N and O is reported. These compounds were evaluated in vitro against four parasites (Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi Tulahuen C2C4, Leishmania donovani MHOM-ET-67/L82 axenic amastigotes, and Plasmodium falciparum K1 strain), against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc(2)155 and Corynebacterium glutamicum ATCC13032, and cytotoxicity was determined against L6 rat myoblast cells. Nostocarboline and derivatives displayed potent and selective in vitro inhibition of P. falciparum with weak cytotoxicity. The dimers displayed submicromolar inhibition of L. donovani and T. brucei, and nanomolar activity against P. falciparum, albeit with pronounced cytotoxicity. One dimer showed a MIC(99) value against M. tuberculosis of 2.5 microg/ml. The alkylated eudistomin N and O derivatives displayed activities down to 18 nM against P. falciparum for N-Me Eudistomin N. Four dimers, nostocarboline and three eudostomin derivatives were evaluated in an in vivo Plasmodium berghei mouse model. No significant activity was observed for the dimers, but a 50% reduction in parasitaemia was observed at 4 x 50 mg/kg ip for nostocarboline.
000151178 6531_ $$aNatural products
000151178 6531_ $$aMalaria
000151178 6531_ $$aAntiplasmodial agents
000151178 6531_ $$aCyanobacterial Alkaloid Nostocarboline
000151178 6531_ $$aBeta-Carbolinium Cations
000151178 6531_ $$aAntiplasmodial Activity
000151178 6531_ $$aCryptolepine Analogs
000151178 6531_ $$aNatural-Products
000151178 6531_ $$aAntiprotozoal Agents
000151178 6531_ $$aPotent
000151178 6531_ $$aMarine
000151178 6531_ $$aSalts
000151178 6531_ $$aOrigin
000151178 700__ $$aBonazzi, Simone
000151178 700__ $$aBarbaras, Damien
000151178 700__ $$aPatiny, Luc
000151178 700__ $$aScopelliti, Rosario
000151178 700__ $$aSchneider, Patricia
000151178 700__ $$0243892$$aCole, Stewart T$$g177247
000151178 700__ $$aKaiser, Marcel
000151178 700__ $$aBrun, Reto
000151178 700__ $$aGademann, Karl
000151178 773__ $$j18$$k4$$q1464-76$$tBioorganic & medicinal chemistry
000151178 909C0 $$0252302$$pUPCOL$$xU11742
000151178 909CO $$ooai:infoscience.tind.io:151178$$pSV$$particle
000151178 937__ $$aEPFL-ARTICLE-151178
000151178 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000151178 980__ $$aARTICLE