似我萌investigated were all prepared in the form of hydrochlo-ride by the usual methods before use.The results were summarized in Table1.
As shown in Table1,most studied compounds showed signi?cant cytotoxic activities against several human tu-mor cell lines.9-Substituted harmines,b-carbolines,b-carboline-3-carboxylates,and b-carboline-3-carboxylic acids(except5d,6f,and7d)displayed more remarkable cytotoxic activities than their parent compounds,respec-tively,indicating that the introduction of an appropriate alkyl or benzyl group into9-position of b-carboline ring system facilitates the increase of their cytotoxic activi-ties.
Among all the compounds investigated,9-substituted harmine series demonstrated the highest cytotoxicities while9-substituted butyl b-carboline-3-carboxylates7a, 7c,7d(except7b),and their corresponding parent com-pound7were found to be less active with IC50values of more than100l M against tumor cell lines,suggesting that the substitution of7-methoxy and1-methyl groups might contribute to their increased cytotoxic activities while a long chain alkoxy at3-position might not be pared with the IC50values of other com-pounds,the IC50values of the compounds2a,2b,2f, and2g was lower than50l M,which implicated that the alkyl and benzyl substituents had almost equal po-tency to enhance their cytotoxic activities in vitro.
As for the harmine series,the compound2b with an ethyl group at9-position exhibited the highest cytotoxic activities(except for Lovo cell line).The compound2a having a methyl at position-9showed selective cytotoxic activities against the screened tumor cell lines with the lowest IC50value(8l M)against Hela.The compounds 2f and2g with a penta?uorobenzyl and a phenylpropyl at position-9,respectively,demonstrated the prominent
Table1.Cytotoxicity of b-carboline derivatives in vitro c(IC50,a l M)
Compounds PLA-801b HepG2b Bel-7402b BGC-823b Hela b Lovo b Harmine454654686066
2a29166352843
2b2214284517170
2c1116258692887
2d783132442042527
2e6585579527052
2f424643222831
2g503644462427 31722837927435335
4a219102302204327220
4b130167311171234159
4c1339916410188134
4d124107777348123 5295241293278100160
5a125119195181181175
5b251171247917107
5c136464433310289166
5d>1000>1000>1000>1000>1000312 6275>1000>1000>1000567>1000
6a17010
826014113669
6b8710910710813777
6c71476784760487173
6d7838453813122
6e471169527837
6f>1000>1000387>1000>1000>1000 7>1000>1000>1000>1000>1000>1000
7a675266313394295104
7b1097074826783
7c>1000>1000>10007295445
7d994>1000>1000>1000>1000>1000 8327354369330262198
8a2671472261268988
8b21217913016318362
8c9273921166011
8d100102112528641
8e863161354413
8f573153281005
a Cytotoxicity as IC
50
for each cell line,is the concentration of compound,which reduced by50%the optical density of treated cells with respect to untreated cells using the MTT assay.
b Cell lines include nonsmall cell lung carcinoma(PLA-801),liver carcinoma(HepG2and Bel-7402),gastri
c carcinoma(BGC-823),cervical carci-noma(Hela),colon carcinoma(Lovo).
c Data represent the mean values of three independent determinations.
R.Cao et al./Bioorg.Med.Chem.12(2004)4613–46234615
