Epigallocatechin gallate and curcumin inhibit Bcl-2 - a pharmacophore and docking based approach against cancer

Sep 21, 2026

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The protein Bcl-2 is recognized for its anti-apoptotic role and its involvement in cancer progression, motivating strategies that suppress Bcl-2 to promote cellular death. This study builds a pharmacophore model to screen Traditional Chinese Medicine (TCM) databases, selecting compounds with fitness scores above 0.75. ADMET filtering identifies six promising candidates, followed by XP docking, MM-GBSA free-energy estimation, and 100 ns molecular dynamics for curcumin and EGCG, showing EGCG-bound Bcl-2 inhibition potential.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

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Introduction

Bahadar etal. Breast Cancer Research (2024) 26:114 Breast Cancer Research [https://doi.org/10.1186/s13058-024-01868-9](https://doi.org/10.1186/s13058-024-01868-9) RESEARCH Open Access Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer Noor Bahadar 1,2, Sher Bahadar3, Abdul Sajid3, Muqeet Wahid4, Ghadir Ali5, Abdullah Alghamdi6, Hakeem Zada7, Tamreez Khan3, Shafqat Ullah3 and Qingjia Sun 1* Abstract The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM) . Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gal late (EGCG) . The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions. Keywords Bcl-2, EGCG, Curcumin, Pharmacophore modeling, Molecular docking *Correspondence: Qingjia Sun [web14dd@jlu.edu.cn](web14dd@jlu.edu.cn) 1Department of Otorhinolaryngology, Head and Neck Surgery, The China-Japan Union Hospital of Jilin University, Xiantai Street 126, 130033, Changchun, Jilin, China 2Key Laboratory of Molecular Epigenetics ofthe Ministry of Education (MOE), School of Life Sciences, Northeast Normal University, Renmin Street, Changchun, Jilin 130024, China 3College of Veterinary Sciences and Animal Husbandry, Abdul Wali Khan University Mardan, Mardan, Khyber Pakhtunkhwa, Pakistan 4Department of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan 5Department of Life Sciences, School of Science, University of Management and Technology (UMT), Lahore 54700, Pakistan 6Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia 7Mubarak Diagnostic Laboratory and Research Center, Peshawar, Pakistan © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If

FAQs

What is the study’s main therapeutic target and why?

The study targets the anti-apoptotic protein Bcl-2, which is implicated in cancer progression. Suppressing Bcl-2 is proposed as a way to promote cellular death in malignancies.

How were potential compounds selected from the TCM database?

A pharmacophore model was constructed and used to search the TCM database. Compounds with fitness scores above 0.75 were selected, then ADMET analysis filtered candidates for favorable properties.

What computational methods were used to evaluate ligand–Bcl-2 interactions?

The pipeline includes XP docking to rank candidates, MM-GBSA to estimate overall free binding energy, and 100 ns molecular dynamics simulations to assess binding stability for curcumin and EGCG.

What conclusion did the study reach about EGCG and Bcl-2?

The findings indicate identification of a molecular structure that effectively inhibits Bcl-2 function when bound to EGCG, suggesting a potential route for developing drugs relevant to both inflammatory and tumorous conditions.

Sep 21, 2026

Uploaded by Violet