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Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential

A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking a...

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Autores principales: Asif, Mohd, Alvi, Sahir Sultan, Azaz, Tazeen, Khan, Abdul Rahman, Tiwari, Bhoopendra, Hafeez, Bilal Bin, Nasibullah, Malik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139052/
https://www.ncbi.nlm.nih.gov/pubmed/37108498
http://dx.doi.org/10.3390/ijms24087336
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author Asif, Mohd
Alvi, Sahir Sultan
Azaz, Tazeen
Khan, Abdul Rahman
Tiwari, Bhoopendra
Hafeez, Bilal Bin
Nasibullah, Malik
author_facet Asif, Mohd
Alvi, Sahir Sultan
Azaz, Tazeen
Khan, Abdul Rahman
Tiwari, Bhoopendra
Hafeez, Bilal Bin
Nasibullah, Malik
author_sort Asif, Mohd
collection PubMed
description A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking analysis revealed that among all derivatives of SOXs (4a–4h), 4a has a substantial binding affinity (∆G) −6.65, −6.55, −8.73, and −7.27 Kcal/mol with CD-44, EGFR, AKR1D1, and HER-2, respectively. A functional study demonstrated that SOX 4a has a substantial impact on human cancer cell phenotypes exhibiting abnormality in cytoplasmic and nuclear architecture as well as granule formation leading to cell death. SOX 4a treatment robustly induced reactive oxygen species (ROS) generation in cancer cells as observed by enhanced DCFH-DA signals. Overall, our results suggest that SOX (4a) targets CD-44, EGFR, AKR1D1, and HER-2 and induces ROS generation in cancer cells. We conclude that SOX (4a) could be explored as a potential chemotherapeutic molecule against various cancers in appropriate pre-clinical in vitro and in vivo model systems.
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spelling pubmed-101390522023-04-28 Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential Asif, Mohd Alvi, Sahir Sultan Azaz, Tazeen Khan, Abdul Rahman Tiwari, Bhoopendra Hafeez, Bilal Bin Nasibullah, Malik Int J Mol Sci Article A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking analysis revealed that among all derivatives of SOXs (4a–4h), 4a has a substantial binding affinity (∆G) −6.65, −6.55, −8.73, and −7.27 Kcal/mol with CD-44, EGFR, AKR1D1, and HER-2, respectively. A functional study demonstrated that SOX 4a has a substantial impact on human cancer cell phenotypes exhibiting abnormality in cytoplasmic and nuclear architecture as well as granule formation leading to cell death. SOX 4a treatment robustly induced reactive oxygen species (ROS) generation in cancer cells as observed by enhanced DCFH-DA signals. Overall, our results suggest that SOX (4a) targets CD-44, EGFR, AKR1D1, and HER-2 and induces ROS generation in cancer cells. We conclude that SOX (4a) could be explored as a potential chemotherapeutic molecule against various cancers in appropriate pre-clinical in vitro and in vivo model systems. MDPI 2023-04-15 /pmc/articles/PMC10139052/ /pubmed/37108498 http://dx.doi.org/10.3390/ijms24087336 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Asif, Mohd
Alvi, Sahir Sultan
Azaz, Tazeen
Khan, Abdul Rahman
Tiwari, Bhoopendra
Hafeez, Bilal Bin
Nasibullah, Malik
Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title_full Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title_fullStr Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title_full_unstemmed Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title_short Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
title_sort novel functionalized spiro [indoline-3,5′-pyrroline]-2,2′dione derivatives: synthesis, characterization, drug-likeness, adme, and anticancer potential
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139052/
https://www.ncbi.nlm.nih.gov/pubmed/37108498
http://dx.doi.org/10.3390/ijms24087336
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