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Insight into in vitro thymidine phosphorylase and in silico molecular docking studies: identification of hybrid thiazole bearing Schiff base derivatives

  • Sundas Mumtaz , Fazal Rahim EMAIL logo , Rafaqat Hussain ORCID logo EMAIL logo , Shoaib Khan ORCID logo , Obaid Ur Rahman Abid , Asma Sardar , Tayyiaba Iqbal , Mohammad Shahidul Islam and Tahani Mazyad Almutairi
Published/Copyright: February 6, 2025
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Zeitschrift für Naturforschung C
From the journal Zeitschrift für Naturforschung C Volume 80 Issue 9-10

Abstract

In pursuit of effective thymidine phosphorylase inhibitors, a series of hybrid analogs of thiazole-hydrazone derivatives (1–15) were synthesized and evaluated for their enzyme inhibitory potential using 7-deazaxanthine as a positive control. The goal was to determine these derivatives’ effectiveness in suppressing thymidine phosphorylase activity, a target relevant to antitumor strategies due to the enzyme’s role in angiogenesis and tumor growth. Biological evaluations indicated that all synthesized analogs displayed significant to moderate inhibitory activity, with IC50 values between 3.93 ± 0.90 and 25.75 ± 4.30 µM. Particularly, compounds 12, 9, and 28 exhibited superior potency, with IC50 values of 3.93 ± 0.90, 4.10 ± 1.10, and 4.50 ± 1.10 µM, respectively, surpassing the standard inhibitor 7-deazaxanthine (IC50 = 16.8 ± 2.20 µM). Additionally, molecular docking studies were performed to elucidate the binding interactions of the synthesized thiazole-hydrazone derivatives with the active site of thymidine phosphorylase. The docking results aligned well with experimental data, revealing favorable binding conformations and significant interactions that support the observed inhibitory activities, particularly in the most potent compounds. These findings underscore the promise of thiazole-hydrazone derivatives as effective thymidine phosphorylase inhibitors, suggesting that targeted structural modifications could further enhance their activity. Further investigations, including in vivo studies, are warranted to explore their potential applications in anticancer therapies. This study highlights the valuable role of molecular docking in understanding the structure–activity relationship (SAR) of thiazole-hydrazone derivatives, emphasizing the potential of these compounds in advancing thymidine phosphorylase inhibition strategies for therapeutic purposes.

Keywords: synthesis; thiazole; thymidine phosphorylase; SAR and molecular docking
Corresponding authors: Fazal Rahim, Department of Chemistry, Hazara University, Mansehra, 21120, Pakistan; and Rafaqat Hussain, College of Biology, Hunan University Changsha, Hunan 81002 P.R. China, E-mail: (F. Rahim), (R. Hussain)

Funding source: King Saud University, Riyadh, Saudi Arabia

Award Identifier / Grant number: RSP2025R273

  1. Research ethics: The conducted research is not related to either human or animal use.

  2. Informed consent: Not applicable.

  3. Author contributions: Sundas Mumtaz: writing – original draft. Fazal Rahim and Obaid Ur Rahman Abid supervision. Rafaqat Hussain: writing – review and editing. Shoaib Khan: methodology and investigation. Asma Sardar: visualization and software. Tayyiaba Iqbal formal analysis. Mohammad Shahidul Islam & Tahani Mazyad Almutairi: writing – review and editing.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors declare no conflict of interest.

  6. Research funding: The research was financially supported by Researchers Supporting Project number (RSP2025R273), King Saud University, Riyadh, Saudi Arabia.

  7. Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2024-0214).

Received: 2024-10-01
Accepted: 2025-01-18
Published Online: 2025-02-06
Published in Print: 2025-09-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/znc-2024-0214
Keywords for this article
synthesis; thiazole; thymidine phosphorylase; SAR and molecular docking

Articles in the same Issue

  1. Frontmatter
  2. Review Articles
  3. Phyto-pharmaceuticals as a safe and potential alternative in management of psoriasis: a review
  4. Latest developments in biomaterial interfaces and drug delivery: challenges, innovations, and future outlook
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