Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs
Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoqui...
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MDPI AG
2024-03-01
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author | Yo Kiichi Koshiro Fukuoka Anna Kitano Koya Ishino Naoyuki Kotoku |
author_facet | Yo Kiichi Koshiro Fukuoka Anna Kitano Koya Ishino Naoyuki Kotoku |
author_sort | Yo Kiichi |
collection | DOAJ |
description | Makaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at <i>N</i>-5 and <i>N</i>-9 yielded makaluvamine J and several analogs. A structure–activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at <i>N</i>-9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at <i>N</i>-5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog <b>24</b> showed potent and selective cytotoxicity (IC<sub>50</sub> = 0.029 µM, selective index = 13.1), exceeding those of natural products. |
first_indexed | 2024-04-24T17:58:44Z |
format | Article |
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language | English |
last_indexed | 2024-04-24T17:58:44Z |
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spelling | doaj.art-d58e9ac208d54d97abc5b30539cc7b3b2024-03-27T13:57:15ZengMDPI AGMolecules1420-30492024-03-01296138910.3390/molecules29061389Unified Synthesis and Biological Evaluation of Makaluvamine J and Its AnalogsYo Kiichi0Koshiro Fukuoka1Anna Kitano2Koya Ishino3Naoyuki Kotoku4College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, JapanCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, JapanCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, JapanCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, JapanCollege of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, JapanMakaluvamine J, a pyrroloiminoquinone alkaloid of marine sponge origin, and its analogs were synthesized and assessed for their potential to develop as a novel and selective growth inhibitor targeting human pancreatic cancer PANC-1 cells. Ts-damirone B, a common precursor featuring a pyrroloiminoquinone core structure, was synthesized through Bartoli indole synthesis and IBX-mediated oxidation. Late-stage diversification at <i>N</i>-5 and <i>N</i>-9 yielded makaluvamine J and several analogs. A structure–activity relationship (SAR) analysis highlighted the significance of the lipophilic side chain at <i>N</i>-9 for the growth inhibitory activity of PANC-1 cells. The modest alkyl group at <i>N</i>-5 was found to improve selectivity against other cancer cells. Among the prepared analogs, the tryptamine analog <b>24</b> showed potent and selective cytotoxicity (IC<sub>50</sub> = 0.029 µM, selective index = 13.1), exceeding those of natural products.https://www.mdpi.com/1420-3049/29/6/1389Makaluvamine Jpancreatic canceranalog synthesisstructure-activity relationship |
spellingShingle | Yo Kiichi Koshiro Fukuoka Anna Kitano Koya Ishino Naoyuki Kotoku Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs Molecules Makaluvamine J pancreatic cancer analog synthesis structure-activity relationship |
title | Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs |
title_full | Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs |
title_fullStr | Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs |
title_full_unstemmed | Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs |
title_short | Unified Synthesis and Biological Evaluation of Makaluvamine J and Its Analogs |
title_sort | unified synthesis and biological evaluation of makaluvamine j and its analogs |
topic | Makaluvamine J pancreatic cancer analog synthesis structure-activity relationship |
url | https://www.mdpi.com/1420-3049/29/6/1389 |
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