Exploring Novel Coumarin-Tethered Bis-Triazoles - Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular Modelling Investigations

Sep 21, 2026

Two newly synthesized coumarin-tethered bis-triazole compounds, 7c and 9f, were identified as inducers of apoptosis in human pancreatic cells (PANC-1) through a caspase 3/7-mediated pathway. Both compounds showed ~100-fold improved potency over Gemcitabine (IC50 = 7.15 ± 1.19 and 6.09 ± 0.79 µM vs >500 µM) and did not exhibit toxicity toward normal pancreatic epithelial cells (H6C7). Molecular docking supported strong hydrogen-bonding interactions with EGFR, and moderate antimicrobial activity against a microbial strain panel.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Rationale for new anticancer and antimicrobial agents

Apoptosis and caspase signaling

Coumarin and triazole scaffolds in drug discovery

ChemMedChem Research Article [doi.org/10.1002/cmdc.202400297](doi.org/10.1002/cmdc.202400297) [www.chemmedchem.org](www.chemmedchem.org) Exploring Novel Coumarin-Tethered Bis-Triazoles: Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular Modelling Investigations Sanjeev Dhawan,[a] Ashona Singh,[a] Neha Manhas,[a] Pule Seboletswe,[a] Lungisani Khubone,[a] Gobind Kumar,[a] Sreekantha B. Jonnalagadda,[a] Asif Raza,[b] Arun K. Sharma,[b] and Parvesh Singh*[a] In the present study, we identified that two representative compounds (7 c and 9 f) of our newly synthesized coumarintagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7 c and 9 f (IC50 = 7.15 􀀆 1.19 and 6.09 􀀆0.79 μM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC50 = > 500 μM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7) . Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7 c and 9 f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer. Introduction Cancer is one of the leading causes of death globally, and discovering new therapeutic approaches is a priority in drug discovery. [1] Pancreatic cancer is expected to overtake breast and colorectal cancer as the second leading cause of death in developing countries over the next decade, posing a significant challenge to the medical and scientific communities.[2] As a highly aggressive cancer, the available treatments are largely ineffective. Subsequently, traditional treatments such as radiotherapy and chemotherapy are less effective and have no desired effect on tumor growth. [3] Therefore, effective chemotherapeutic agents are urgently required to treat this disease. Atthe moment, one of the strategies being used to treat cancer is combination chemotherapy involving several mechanisms of action.[4] [a] S. Dhawan, A. Singh, N. Manhas, P. Seboletswe, L. Khubone, G. Kumar, S. B. Jonnalagadda, P. Singh School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000 South Africa [E-mail: parveshdurban@gmail.com](E-mail: parveshdurban@gmail.com)[ ](E-mail: parveshdurban@gmail.com)[b] A. Raza, A. K. Sharma Department of Pharmacology; Penn State College of Medicine, Penn State Cancer Institute, CH72; 500 University Drive, Hershey, PA 17033, USA Supporting information for this article is available on the WWW under [https://doi.org/10.1002/cmdc.202400297](https://doi.org/10.1002/cmdc.202400297) © 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. Microbial infection is another serious problem that continues to pose a significant threat to human life due to the emergence of resistance to currently available antibiotic artillery, and thus has become a seriously growing public health concern. [5] As a consequence, the discovery of new antimicrobial agents with potent activity against drug-resistant microbes is of paramount importance.[6] This underscores the importance of ongoing research into anticancer and antimicrobial agents. [7] The multi-functionalized coumarin scaffold signifies a class of heterocyclic compounds with considerable pharmacologica

FAQs

Which compounds and cell model were investigated for apoptosis induction?

The study evaluated coumarin-tethered bis-triazole compounds 7c and 9f in human pancreatic cancer cells PANC-1.

How were apoptosis effects mechanistically assessed?

Apoptosis induction was mediated via the caspase 3/7 pathway.

What evidence supports target relevance and selectivity?

Molecular docking indicated strong hydrogen bonding with EGFR, and the compounds showed no toxicity to normal pancreatic epithelial cells (H6C7).

Sep 21, 2026

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