Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti-Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies

Sukhmeet Kaur; Jasneet Kaur; Kirandeep Kaur; Raghav Mahajan; Jyotisina; Kulwinder Kaur

doi:10.2174/012210299X310595240626104426

ISSN: 2210-299X
E-ISSN: 2210-3007

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oa Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti-Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies
Authors: Sukhmeet Kaur¹, Jasneet Kaur¹, Kirandeep Kaur¹, Raghav Mahajan¹, Jyotisina¹ and Kulwinder Kaur²
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¹ Department of Chemistry, Khalsa College Amritsar, Amritsar, India ² Royal College of Surgeons in Ireland, Dublin, Ireland
Source: Current Indian Science, Volume 2, Issue 1, Jan 2024, e2210299X310595
DOI: https://doi.org/10.2174/012210299X310595240626104426
- Received: 27 Mar 2024
- Accepted: 05 Jun 2024
- Available online: 03 Jul 2024

Abstract

Aim

This study aims to explore the binding interactions between synthesized 3,3’-Disubstituted Oxindoles and the HCK enzyme, with the specific goal of discovering potential anticancer agents.

Background

Cancer presents an ongoing global health challenge, necessitating the exploration of innovative therapeutic approaches. Isatin derivatives and pyridine compounds hold great promise for the development of anticancer drugs due to their wide-ranging biological activities. Moreover, HCK plays a significant role in chemotherapy resistance and reduced drug efficacy in clinical settings, highlighting its importance in the intricate network of cancer pathophysiology. There is an urgent need for targeted interventions to regulate HCK activity and enhance cancer treatment outcomes.

Methods

In our study, we ensured meticulous optimization of protein and ligand preparation to guarantee accurate docking simulations. We conducted molecular docking analyses using the state-of-the-art Glide module and assessed ADME properties using the Schrödinger suite's QikProp tool.

Results

Through molecular docking, compounds 3c and 3e have emerged as promising anticancer agents with low docking scores against Tyrosine Kinase. Further ADME analysis has provided valuable insights into the compounds' in-silico behaviour, while computed dipole moments have enhanced our understanding of their physicochemical characteristics.

Conclusion

In this study, we explored how the synthesized compounds bind within the HCK active site, indicating potential anticancer properties. Through in silico docking, we identified compounds 3c and 3e as possible anticancer agents, with the lowest docking scores of -7.621 and -7.602 kcal/mol against Tyrosine Kinase. These findings emphasize the importance of computational approaches in drug discovery and offer valuable insights for future research and development efforts.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti-Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies

Curr. Indian Sci. 2, e2210299X310595 (2024); https://doi.org/10.2174/012210299X310595240626104426

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Supplementary material is available on the publisher’s website along with the published article.

Article Type: Research Article

Keyword(s): ADME studies; Inhibitors; Molecular docking; Oxindoles; Potential anti-cancer; Tyrosine kinase

oa Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti-Cancer Tyrosine Kinase Inhibitors-molecular Docking and ADME Studies

Abstract

From This Site

Supplementary material is available on the publisher’s website along with the published article.

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