Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights

M. Shaheer Malik; Hissana Ather; Shaik Mohammad Asif Ansari; Ayesha Siddiqua; Qazi Mohammad Sajid Jamal; Ali H. Alharbi; Munirah M. Al-Rooqi; Rabab S. Jassas; Essam M. Hussein; Ziad Moussa; Rami J. Obaid; Saleh A. Ahmed

doi:10.3390/ph16030333

Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights

M. Shaheer Malik, Hissana Ather, Shaik Mohammad Asif Ansari, Ayesha Siddiqua, Qazi Mohammad Sajid Jamal, Ali H. Alharbi, Munirah M. Al-Rooqi, Rabab S. Jassas, Essam M. Hussein, Ziad Moussa, Rami J. Obaid, Saleh A. Ahmed

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60–65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC₅₀ values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

Original language	English
Article number	333
Journal	Pharmaceuticals
Volume	16
Issue number	3
DOIs	https://doi.org/10.3390/ph16030333
Publication status	Published - Mar 2023

Keywords

ADME
anti-cancer activity
chromenes
indole
molecular docking
multicomponent reaction

ASJC Scopus subject areas

Molecular Medicine
Pharmaceutical Science
Drug Discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ph16030333

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@article{7f668cfda99747858276f724d7af5c39,

title = "Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights",

abstract = "Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60–65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.",

keywords = "ADME, anti-cancer activity, chromenes, indole, molecular docking, multicomponent reaction",

author = "Malik, {M. Shaheer} and Hissana Ather and {Asif Ansari}, {Shaik Mohammad} and Ayesha Siddiqua and Jamal, {Qazi Mohammad Sajid} and Alharbi, {Ali H.} and Al-Rooqi, {Munirah M.} and Jassas, {Rabab S.} and Hussein, {Essam M.} and Ziad Moussa and Obaid, {Rami J.} and Ahmed, {Saleh A.}",

note = "Funding Information: The authors would like to acknowledge the Deanship of Scientific Research at King Khalid University, Saudi Arabia, for funding this project through the Small Group Program (Grant No. RGP-1/30/43). Publisher Copyright: {\textcopyright} 2023 by the authors.",

year = "2023",

month = mar,

doi = "10.3390/ph16030333",

language = "English",

volume = "16",

journal = "Pharmaceuticals",

issn = "1424-8247",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "3",

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TY - JOUR

T1 - Novel Indole-Tethered Chromene Derivatives

T2 - Synthesis, Cytotoxic Properties, and Key Computational Insights

AU - Malik, M. Shaheer

AU - Ather, Hissana

AU - Asif Ansari, Shaik Mohammad

AU - Siddiqua, Ayesha

AU - Jamal, Qazi Mohammad Sajid

AU - Alharbi, Ali H.

AU - Al-Rooqi, Munirah M.

AU - Jassas, Rabab S.

AU - Hussein, Essam M.

AU - Moussa, Ziad

AU - Obaid, Rami J.

AU - Ahmed, Saleh A.

N1 - Funding Information: The authors would like to acknowledge the Deanship of Scientific Research at King Khalid University, Saudi Arabia, for funding this project through the Small Group Program (Grant No. RGP-1/30/43). Publisher Copyright: © 2023 by the authors.

PY - 2023/3

Y1 - 2023/3

N2 - Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60–65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

AB - Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60–65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

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KW - anti-cancer activity

KW - chromenes

KW - indole

KW - molecular docking

KW - multicomponent reaction

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Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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