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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A plant-derived neocryptolepine core, the 5-Me-indolo[2,3-b]quinoline skeleton, was emblazoned with substituents at C11 and C2 and then tested against various cancer cell lines to find potent anticancer agents. In the in vitro antiproliferative activity assay against the breast cancer MDA-MB-453 cell line, the attachment of alkylamino substituents at C11 of the 5-Me-indolo[2,3-b]quinoline induced improved activities. Specifically, 11-(3-aminopropylamino) and 11-(4-aminobutylamino) derivatives indicated the highest activity and selectivity against MDA-MB-453 (IC50 = 0.3-0.5 μM) and also exhibited a higher cytotoxicity against the colon adenocarcinoma (WiDr) and ovarian cancer (SKOv3) cell lines. A synergistic effect by attachment of substituents at C2 was favorably observed with an electron-donating group, such as CH3O, and unfavorably observed with an electron-withdrawing one, such as F and CF3. Further modification of the terminal free amino group of the lariat attachment at C11 into the corresponding acylamides and 2,3-dihydrobenzo[e][1,3]thiazin-4-ones was not effective for the antiproliferative activity. The computer-assisted database analysis, COMPARE, suggested that 14e and 13b have a mode of action similar to actinomycin D and 13c has a mode of actions similar to vindesine sulfate or aclarubicin hydrochloride. However, the new compounds may have other unique mode of actions since the correlation coefficients (r) were in relatively low levels.

Original languageEnglish
Pages (from-to)879-892
Number of pages14
JournalMedicinal Chemistry Research
Volume25
Issue number5
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Quinolines
Cell growth
Cells
Cell Line
Growth
Aclarubicin
Vindesine
Electrons
Neoplasms
Dactinomycin
Cytotoxicity
Skeleton
Antineoplastic Agents
Ovarian Neoplasms
Inhibitory Concentration 50
Assays
Colon
Adenocarcinoma
Databases
Breast Neoplasms

Keywords

  • 5Me-indolo[2,3-b]quinoline
  • Antiproliferative agent
  • C11-alkylamino-substituted
  • COMPARE study
  • JFCR39 panel
  • MDA-MB-453

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

Cite this

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 Wu; Imran Hossain, Md; Wang, Li; Tominaga, Taihei; Takebayashi, Takeshi; Murakami, Masaharu; Yasuda, Mizuki; Shigehiro, Tsukasa; Kasai, Tomonari; Mizutani, Akifumi; Murakami, Hiroshi; El Sayed, Ibrahim El Tantawy; Dan, Shingo; Yamori, Takao; Seno, Masaharu; Inokuchi, Tsutomu.

In: Medicinal Chemistry Research, Vol. 25, No. 5, 01.05.2016, p. 879-892.

Research output: Contribution to journalArticle

Okada, M, Mei, ZW, Imran Hossain, M, Wang, L, Tominaga, T, Takebayashi, T, Murakami, M, Yasuda, M, Shigehiro, T, Kasai, T, Mizutani, A, Murakami, H, El Sayed, IET, Dan, S, Yamori, T, Seno, M & Inokuchi, T 2016, 'Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses', Medicinal Chemistry Research, vol. 25, no. 5, pp. 879-892. https://doi.org/10.1007/s00044-016-1508-z
Okada, Masashi ; Mei, Zhen Wu ; Imran Hossain, Md ; Wang, Li ; Tominaga, Taihei ; Takebayashi, Takeshi ; Murakami, Masaharu ; Yasuda, Mizuki ; Shigehiro, Tsukasa ; Kasai, Tomonari ; Mizutani, Akifumi ; Murakami, Hiroshi ; El Sayed, Ibrahim El Tantawy ; Dan, Shingo ; Yamori, Takao ; Seno, Masaharu ; Inokuchi, Tsutomu. / Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses. In: Medicinal Chemistry Research. 2016 ; Vol. 25, No. 5. pp. 879-892.
@article{c50d9fe7acca4ca39a112cbd7fae564c,
title = "Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses",
abstract = "A plant-derived neocryptolepine core, the 5-Me-indolo[2,3-b]quinoline skeleton, was emblazoned with substituents at C11 and C2 and then tested against various cancer cell lines to find potent anticancer agents. In the in vitro antiproliferative activity assay against the breast cancer MDA-MB-453 cell line, the attachment of alkylamino substituents at C11 of the 5-Me-indolo[2,3-b]quinoline induced improved activities. Specifically, 11-(3-aminopropylamino) and 11-(4-aminobutylamino) derivatives indicated the highest activity and selectivity against MDA-MB-453 (IC50 = 0.3-0.5 μM) and also exhibited a higher cytotoxicity against the colon adenocarcinoma (WiDr) and ovarian cancer (SKOv3) cell lines. A synergistic effect by attachment of substituents at C2 was favorably observed with an electron-donating group, such as CH3O, and unfavorably observed with an electron-withdrawing one, such as F and CF3. Further modification of the terminal free amino group of the lariat attachment at C11 into the corresponding acylamides and 2,3-dihydrobenzo[e][1,3]thiazin-4-ones was not effective for the antiproliferative activity. The computer-assisted database analysis, COMPARE, suggested that 14e and 13b have a mode of action similar to actinomycin D and 13c has a mode of actions similar to vindesine sulfate or aclarubicin hydrochloride. However, the new compounds may have other unique mode of actions since the correlation coefficients (r) were in relatively low levels.",
keywords = "5Me-indolo[2,3-b]quinoline, Antiproliferative agent, C11-alkylamino-substituted, COMPARE study, JFCR39 panel, MDA-MB-453",
author = "Masashi Okada and Mei, {Zhen Wu} and {Imran Hossain}, Md and Li Wang and Taihei Tominaga and Takeshi Takebayashi and Masaharu Murakami and Mizuki Yasuda and Tsukasa Shigehiro and Tomonari Kasai and Akifumi Mizutani and Hiroshi Murakami and {El Sayed}, {Ibrahim El Tantawy} and Shingo Dan and Takao Yamori and Masaharu Seno and Tsutomu Inokuchi",
year = "2016",
month = "5",
day = "1",
doi = "10.1007/s00044-016-1508-z",
language = "English",
volume = "25",
pages = "879--892",
journal = "Medicinal Chemistry Research",
issn = "1054-2523",
publisher = "Birkhause Boston",
number = "5",

}

TY - JOUR

T1 - Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses

AU - Okada, Masashi

AU - Mei, Zhen Wu

AU - Imran Hossain, Md

AU - Wang, Li

AU - Tominaga, Taihei

AU - Takebayashi, Takeshi

AU - Murakami, Masaharu

AU - Yasuda, Mizuki

AU - Shigehiro, Tsukasa

AU - Kasai, Tomonari

AU - Mizutani, Akifumi

AU - Murakami, Hiroshi

AU - El Sayed, Ibrahim El Tantawy

AU - Dan, Shingo

AU - Yamori, Takao

AU - Seno, Masaharu

AU - Inokuchi, Tsutomu

PY - 2016/5/1

Y1 - 2016/5/1

N2 - A plant-derived neocryptolepine core, the 5-Me-indolo[2,3-b]quinoline skeleton, was emblazoned with substituents at C11 and C2 and then tested against various cancer cell lines to find potent anticancer agents. In the in vitro antiproliferative activity assay against the breast cancer MDA-MB-453 cell line, the attachment of alkylamino substituents at C11 of the 5-Me-indolo[2,3-b]quinoline induced improved activities. Specifically, 11-(3-aminopropylamino) and 11-(4-aminobutylamino) derivatives indicated the highest activity and selectivity against MDA-MB-453 (IC50 = 0.3-0.5 μM) and also exhibited a higher cytotoxicity against the colon adenocarcinoma (WiDr) and ovarian cancer (SKOv3) cell lines. A synergistic effect by attachment of substituents at C2 was favorably observed with an electron-donating group, such as CH3O, and unfavorably observed with an electron-withdrawing one, such as F and CF3. Further modification of the terminal free amino group of the lariat attachment at C11 into the corresponding acylamides and 2,3-dihydrobenzo[e][1,3]thiazin-4-ones was not effective for the antiproliferative activity. The computer-assisted database analysis, COMPARE, suggested that 14e and 13b have a mode of action similar to actinomycin D and 13c has a mode of actions similar to vindesine sulfate or aclarubicin hydrochloride. However, the new compounds may have other unique mode of actions since the correlation coefficients (r) were in relatively low levels.

AB - A plant-derived neocryptolepine core, the 5-Me-indolo[2,3-b]quinoline skeleton, was emblazoned with substituents at C11 and C2 and then tested against various cancer cell lines to find potent anticancer agents. In the in vitro antiproliferative activity assay against the breast cancer MDA-MB-453 cell line, the attachment of alkylamino substituents at C11 of the 5-Me-indolo[2,3-b]quinoline induced improved activities. Specifically, 11-(3-aminopropylamino) and 11-(4-aminobutylamino) derivatives indicated the highest activity and selectivity against MDA-MB-453 (IC50 = 0.3-0.5 μM) and also exhibited a higher cytotoxicity against the colon adenocarcinoma (WiDr) and ovarian cancer (SKOv3) cell lines. A synergistic effect by attachment of substituents at C2 was favorably observed with an electron-donating group, such as CH3O, and unfavorably observed with an electron-withdrawing one, such as F and CF3. Further modification of the terminal free amino group of the lariat attachment at C11 into the corresponding acylamides and 2,3-dihydrobenzo[e][1,3]thiazin-4-ones was not effective for the antiproliferative activity. The computer-assisted database analysis, COMPARE, suggested that 14e and 13b have a mode of action similar to actinomycin D and 13c has a mode of actions similar to vindesine sulfate or aclarubicin hydrochloride. However, the new compounds may have other unique mode of actions since the correlation coefficients (r) were in relatively low levels.

KW - 5Me-indolo[2,3-b]quinoline

KW - Antiproliferative agent

KW - C11-alkylamino-substituted

KW - COMPARE study

KW - JFCR39 panel

KW - MDA-MB-453

UR - http://www.scopus.com/inward/record.url?scp=84962978230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962978230&partnerID=8YFLogxK

U2 - 10.1007/s00044-016-1508-z

DO - 10.1007/s00044-016-1508-z

M3 - Article

AN - SCOPUS:84962978230

VL - 25

SP - 879

EP - 892

JO - Medicinal Chemistry Research

JF - Medicinal Chemistry Research

SN - 1054-2523

IS - 5

ER -