Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent

Sana Iqbal; Farhat Firdous; Muhammad Furqan; Aishah Bilal; Salman Fozail; Sebastian Öther Gee Pohl; Nora Julia Doleschall; Kevin B. Myant; Upendra Singh; Abdul Hamid Emwas; Mariusz Jaremko; Amir Faisal; Rahman Shah Zaib Saleem

doi:10.1016/j.bioorg.2023.107094

Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent

Sana Iqbal, Farhat Firdous, Muhammad Furqan, Aishah Bilal, Salman Fozail, Sebastian Öther Gee Pohl, Nora Julia Doleschall, Kevin B. Myant, Upendra Singh, Abdul Hamid Emwas, Mariusz Jaremko, Amir Faisal^*, Rahman Shah Zaib Saleem

^*Corresponding author for this work

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

1 Scopus citations

Abstract

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI₅₀ values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G₂/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

Original language	English (US)
Article number	107094
Journal	Bioorganic Chemistry
Volume	143
DOIs	https://doi.org/10.1016/j.bioorg.2023.107094
State	Published - Feb 2024

Keywords

Anticancer
Bis-amide
Microtubule stabilizing agents
Mouse organoid and human organoid models
Tubulin polymerization

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Drug Discovery
Organic Chemistry

UN SDGs

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

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10.1016/j.bioorg.2023.107094

Cite this

Iqbal, S., Firdous, F., Furqan, M., Bilal, A., Fozail, S., Pohl, S. Ö. G., Doleschall, N. J., Myant, K. B., Singh, U., Emwas, A. H., Jaremko, M., Faisal, A., & Saleem, R. S. Z. (2024). Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent. Bioorganic Chemistry, 143, Article 107094. https://doi.org/10.1016/j.bioorg.2023.107094

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abstract = "Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.",

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author = "Sana Iqbal and Farhat Firdous and Muhammad Furqan and Aishah Bilal and Salman Fozail and Pohl, {Sebastian {\"O}ther Gee} and Doleschall, {Nora Julia} and Myant, {Kevin B.} and Upendra Singh and Emwas, {Abdul Hamid} and Mariusz Jaremko and Amir Faisal and Saleem, {Rahman Shah Zaib}",

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doi = "10.1016/j.bioorg.2023.107094",

language = "English (US)",

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T1 - Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent

AU - Iqbal, Sana

AU - Firdous, Farhat

AU - Furqan, Muhammad

AU - Bilal, Aishah

AU - Fozail, Salman

AU - Pohl, Sebastian Öther Gee

AU - Doleschall, Nora Julia

AU - Myant, Kevin B.

AU - Singh, Upendra

AU - Emwas, Abdul Hamid

AU - Jaremko, Mariusz

AU - Faisal, Amir

AU - Saleem, Rahman Shah Zaib

PY - 2024/2

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N2 - Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

AB - Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

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KW - Bis-amide

KW - Microtubule stabilizing agents

KW - Mouse organoid and human organoid models

KW - Tubulin polymerization

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Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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