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Review
. 2019 Jun 5;24(11):2121.
doi: 10.3390/molecules24112121.

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

Ning Wang  1   2 , Marta Świtalska  3 , Li Wang  4   5 , Elkhabiry Shaban  6   7 , Md Imran Hossain  8   9 , Ibrahim El Tantawy El Sayed  10   11 , Joanna Wietrzyk  12 , Tsutomu Inokuchi  13
Affiliations
Review

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

Ning Wang et al. Molecules. .

Abstract

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.

Keywords: antiproliferative activity; cryptolepine; isocryptolepine; neocryptolepine; structure activity relationships.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of typical indoloquinolines from Cryptolepis sanguinolenta.
Figure 2
Figure 2
Structures of cryptolepine derivatives.
Figure 3
Figure 3
Structure of neocryptolepine derivatives 7, 8, chromeno[2,3-b]indoles 9, and isocryptolepine derivatives 10.
Scheme 1
Scheme 1
Synthesis of 11-aminoalkylamino-5-methylindolo[2,3-b]quinolines.
Figure 4
Figure 4
Structures of artemisinin-neocryptolepine hybrids.
Figure 5
Figure 5
Structure of tacrine-neocryptolepine hybrids.
Figure 6
Figure 6
Growth inhibitory- and cytotoxic activities of compounds (A) 7d, (B) 7k, and (C) 7q across a panel of the JFCR39 cell lines. The mean graph was produced by computer processing of the 50% growth inhibition (GI50) and the 50% lethal concentration (LC50) values. The logarithm of the GI50 and the LC50 values for each cell line is indicated. The X-axis shows the difference on a logarithmic scale between the mean of Log GI50/Log LC50 values for all 39-cell lines (MG-MID, expressed as 0 in the fingerprint) and the Log GI50/Log LC50 for each cell line in the JFCR39 panel. Columns to the right of 0 indicate the sensitivity of the cell lines to a given compound, and columns to the left indicate their resistance. The MG-MID mean of the Log GI50/Log LC50 values for all 39 cell lines; delta difference between the MG-MID and the Log GI50/Log LC50 value for the most sensitive cell line; range difference between the Log GI50/Log LC50 values for the most resistant cell line and the most sensitive cell line.
Figure 6
Figure 6
Growth inhibitory- and cytotoxic activities of compounds (A) 7d, (B) 7k, and (C) 7q across a panel of the JFCR39 cell lines. The mean graph was produced by computer processing of the 50% growth inhibition (GI50) and the 50% lethal concentration (LC50) values. The logarithm of the GI50 and the LC50 values for each cell line is indicated. The X-axis shows the difference on a logarithmic scale between the mean of Log GI50/Log LC50 values for all 39-cell lines (MG-MID, expressed as 0 in the fingerprint) and the Log GI50/Log LC50 for each cell line in the JFCR39 panel. Columns to the right of 0 indicate the sensitivity of the cell lines to a given compound, and columns to the left indicate their resistance. The MG-MID mean of the Log GI50/Log LC50 values for all 39 cell lines; delta difference between the MG-MID and the Log GI50/Log LC50 value for the most sensitive cell line; range difference between the Log GI50/Log LC50 values for the most resistant cell line and the most sensitive cell line.
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