In silico screening of alkaloids as potential inhibitors of epidermal growth factor receptor

Authors

  • Bui Thanh Tung*
  • Pham Thi Kim Dung
  • Nguyen Nhu Son
  • Nguyen Bao Kim
  • Nguyen Hai Ha
  • Nguyen Thanh Tra

Abstract

The epidermal growth factor receptor (EGFR) belongs to the HER/erbB receptor tyrosine kinase (RTK) family, serving as a crucial target for cancer treatment. Anti-EGFR drugs, used as a primary treatment for patients with advanced EGFR gene mutations such as T790M, C797S, and L858R, have shown greater efficacy and safety compared to standard chemotherapy. This study aimed to screen alkaloid compounds with anticancer activity, extracted from the Selleckchem database that inhibit EGFR enzyme activity. The structure of the EGFR receptor was retrieved from the Protein Data Bank, whilst compounds were gathered from the alkaloids library within the Selleckchem database, with their structures downloaded from the PubChem database. Molecular docking was performed using Autodock Vina software. Lipinski’s rule of five was employed to distinguish between compounds with drug-like and non-drug-like properties. The pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Our research indicates that amongst the screened alkaloids, four compounds - peiminine, sanguinarine chloride, dauricine, and irinotecan - are the most promising inhibitors of the EGFR receptor for the treatment of lung cancer. These compounds exhibit high binding affinity for the active sites of EGFR, thus inhibiting its activity. All aforementioned compounds adhere to Lipinski’s rule and possess pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity - ADMET) that render them suitable for development into drugs.

Keywords:

alkaloid, cancer, epidermal growth factor receptor (EGFR), Lipinski’s rule, molecular docking

DOI:

https://doi.org/10.31276/VJSTE.65(3).85-90

Classification number

3.3

Author Biographies

Bui Thanh Tung

University of Medicine and Pharmacy, Vietnam National University-Hanoi, 144 Xuan Thuy Street, Dich Vong Hau Ward, Cau Giay District, Hanoi, Vietnam

Pham Thi Kim Dung

Hanoi Obstetrics and Gynecology Hospital, 929 La Thanh Street, Ngoc Khanh Ward, Ba Dinh District, Hanoi, Vietnam

Nguyen Nhu Son

University of Medicine and Pharmacy, Vietnam National University-Hanoi, 144 Xuan Thuy Street, Dich Vong Hau Ward, Cau Giay District, Hanoi, Vietnam

Nguyen Bao Kim

University of Medicine and Pharmacy, Vietnam National University-Hanoi, 144 Xuan Thuy Street, Dich Vong Hau Ward, Cau Giay District, Hanoi, Vietnam

Nguyen Hai Ha

University of Medicine and Pharmacy, Vietnam National University-Hanoi, 144 Xuan Thuy Street, Dich Vong Hau Ward, Cau Giay District, Hanoi, Vietnam

Nguyen Thanh Tra

Research and Development Department, Phap Viet Xnk and Investment Joint Stock Company (PHAVIMEX), Lane 63, Phu Do Ward, Nam Tu Liem District, Hanoi, Vietnam

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Published

2023-09-15

Received 25 January 2023; revised 14 April 2023; accepted 20 April 2023

How to Cite

Bui Thanh Tung, Pham Thi Kim Dung, Nguyen Nhu Son, Nguyen Bao Kim, Nguyen Hai Ha, & Nguyen Thanh Tra. (2023). In silico screening of alkaloids as potential inhibitors of epidermal growth factor receptor. Vietnam Journal of Science, Technology and Engineering, 65(3), 85-90. https://doi.org/10.31276/VJSTE.65(3).85-90

Issue

Section

Life Sciences