Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses

Okada, Masashi; Mei, Zhen; Hossain, Imran; Wang, Li; Tominaga, Taihei; Takebayashi, Takeshi; Murakami, Masaharu; M, Yasuda; Shigehiro, Tsukasa; Kasai, Tomonari; Mizutani, Akifumi; Murakami, Hiroshi; Sayed, Ibrahim El Tantawy El; Dan, Shingo; Yamori, Takao; Seno, Masaharu; Inokuchi, Tsutomu

doi:10.1007/s00044-016-1508-z

Cited by 13 publications

(8 citation statements)

References 20 publications

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“…The alkaloid, neocryptolepine I or 5-methyl-indolo[3,2-b] quinoline, was isolated recently [ 6 , 7 , 8 ] showed antibacterial, antischistosomicidal, anticancer and antiplasmodial activity [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Further experiments indicated that the anticancer activity of indoloquinolines is based on DNA-binding, specifically by DNA base pair intercalation, followed by inhibition of the enzyme topoisomerase II [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

et al. 2021

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Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

et al. 2021

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“…The results (the means of GI 50 , TGI, and LC 50 values) showed that 7d have potent anticancer activity against the melanoma (LOX-IMVI) and lung (NCIH522, A549, and DMS273) cancer cell lines in the JFCR39 panels. Compound 7d shows a notable cytotoxicity against the breast (BSY-1, LC 50 = 0.82 µM), CNS (SF-539, LC 50 = 0.60 µM, SNB-75, LC 50 = 0.91 µM), colon (HCC2998, LC 50 = 0.74 µM), lung (NCI-H522, LC 50 = 0.71 µM, A549, LC 50 = 0.85, DMS273, LC 50 = 0.70, DMS114, LC 50 = 0.72 µM), and ovarian (VCAR-4, LC 50 = 0.48 µM) cancer cell lines [20].…”

Section: Introductionmentioning

confidence: 99%

Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity

et al. 2019

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Cryptolepine, neocryptolepine and isocryptolepine are naturally occurring indoloquinoline alkaloids with various spectrum of biological properties. Structural modification is an extremely effective means to improve their bioactivities. This review enumerates several neocryptolepine and isocryptolepine analogues with potent antiproliferative activity against MV4-11 (leukemia), A549 (lung cancer), HCT116 (colon cancer) cell lines in vitro. Its activity towards normal mouse fibroblasts BALB/3T3 was also evaluated. Furthermore, structure activity relationships (SAR) are briefly discussed. The anticancer screening of neocryptolepine derivatives was performed in order to determine their cytotoxic and growth inhibitory activities across the JFCR39 cancer cell line panel.

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“…The natural product neocryptolepine ( II ) is known to exhibit prominent antiproliferative activities, for example, IC 50 12.7 ± 1.3 μM against the human (HL-60) leukaemia cell line [ 14 ] and IC 50 7.48 ± 4.42 μM against the human breast cancer MDA-MB-453 cell line [ 20 ], which are comparable with the reference anticancer drug cisplatin (IC 50 7.6 ± 0.7 μM). This antiproliferative activity is improved slightly by introduction of the Cl atom at the C11 of neocryptolepine core to IC 50 5.16 μM.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain

et al. 2017

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Neocryptolepine, which is a kind of tetracyclic indoloquinoline alkaloid, exhibits the inhibition of topoisomerase II and shows antiproliferative activity. The present study describes the synthesis and antiproliferative evaluation of several neocryptolepine analogues carrying a branched, functionalized dibasic side chain at C11. These 2-substituted 5-methyl-indolo[2,3-b]quinoline derivatives were prepared by nucleophilic aromatic substitution (SNAr) of 11-chloroneocryptolepines with appropriate 1,2- and 1,3-diamines. Some of the 11-(ω-aminoalkylamino) derivatives were further transformed into 11-ureido and thioureido analogues. Many of the prepared neocryptolepine derivatives showed submicromolar antiproliferative activity against the human leukemia MV4-11 cell line. Among them, 11-(3-amino-2-hydroxy)propylamino derivatives 2h and 2k were the most cytotoxic with a mean IC50 value of 0.042 μM and 0.057 μM against the MV4-11 cell line, 0.197 μM and 0.1988 μM against the A549 cell line, and 0.138 μM and 0.117 μM against the BALB/3T3 cell line, respectively.

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Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses

Cited by 13 publications

References 20 publications

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid

Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity

Synthesis and In Vitro Antiproliferative Activity of 11-Substituted Neocryptolepines with a Branched ω-Aminoalkylamino Chain

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