1421349-49-6Relevant academic research and scientific papers
In vitro antiproliferative activity of 11-aminoalkylamino-substituted 5H-indolo[2,3-b]quinolines; Improving activity of neocryptolepines by installation of ester substituent
Lu, Wen-Jie,Switalska, Marta,Wang, Li,Yonezawa, Mizuki,El-Sayed, Ibrahim El-Tantawy,Wietrzyk, Joanna,Inokuchi, Tsutomu
, p. 4492 - 4504 (2013)
The research article describes the effect of an ester group on the in vitro antiproliferative activity in SAR studies of 5-methyl-5H-indolo[2,3-b]quinoline (neocryptolepine) derivatives. The C-2 and/or C-9 ester-substituted neocryptolepines were synthesized starting from indole-3-carboxylates and N-methylanilines, which were bearing an ester group. To these ester-substituted neocryptolepines, various aminoalkylamino substituents were further attached at the C-11, and an in vitro antiproliferative assay was performed by varying the substituents at the C-11 and the position of the ester group in the A and/or D ring of neocryptolepines. Results indicated that the antiproliferative activities of the agents could be improved by introducing an ester substituent at the C-9 position. Among them, the methyl 11-(3-aminopropylamino)-5-methyl-5H- indolo[2,3-b]quinoline-9-carboxylate (8b) was the most potent agent with an IC50 value of 0.044 μM against the human leukemia MV4-11 cell line. The selective cytotoxicity of the agents between the cancer cell lines and normal cell lines were also described. The antiproliferative potency of dimethyl 11-(3-aminopropylamino)-5-methyl-5H-indolo[2,3-b]quinoline-2,9- dicarboxylate (9a) against the human colon cancer cell line HCT116 is 28 times higher than against the normal mice fibroblast cell line BALB/3T3. Graphical Abstract: [Figure not available: see fulltext.]
Synthesis and antimalarial testing of neocryptolepine analogues: Addition of ester function in SAR study of 2,11-disubstituted indolo[2,3-b]quinolines
Lu, Wen-Jie,Wicht, Kathryn J.,Wang, Li,Imai, Kento,Mei, Zhen-Wu,Kaiser, Marcel,El Sayed, Ibrahim El Tantawy,Egan, Timothy J.,Inokuchi, Tsutomu
, p. 498 - 511 (2013/07/27)
This report describes the synthesis, and in vitro and in vivo antimalarial evaluations of certain ester-modified neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) derivatives. The modifications were carried out by introducing ester groups at the C2 and/or C9 position on the neocryptolepine core and the terminal amino group of the 3-aminopropylamine substituents at the C11 position with a urea/thiourea unit. The antiplasmodial activities of our derivative agents against two different strains (CQS: NF54, and CQR: K1) and the cytotoxic activity against normal L6 cells were evaluated. The test results showed that the ester modified neocryptolepine derivatives have higher antiplasmodial activities against both strains and a low cytotoxic activity against normal cells. The best results were achieved by compounds 9c and 12b against the NF54 strain with the IC50/SI value as 2.27 nM/361 and 1.81 nM/321, respectively. While against K1 strain, all the tested compounds showed higher activity than the well-known antimalarial drug chloroquine. Furthermore, the compounds were tested for β-haematin inhibition and 12 were found to be more active than chloroquine (IC50 = 18 μM). Structure activity relationship studies exposed an interesting linear correlation between polar surface area of the molecule and β-haematin inhibition for this series. In vivo testing of compounds 7 and 8a against NF54 strain on Plasmodium berghei female mice showed that the introduction of the ester group increased the antiplasmodial activity of the neocryptolepine core substantially.
