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. 2022 Jul 5:2022:5886269.
doi: 10.1155/2022/5886269. eCollection 2022.

Natural Compounds or Their Derivatives against Breast Cancer: A Computational Study

Rajib Hossain  1 , Pranta Ray  2 , Chandan Sarkar  1 , Md Shahazul Islam  1 , Rasel Ahmed Khan  3 , Abul Bashar Ripon Khalipha  1 , Muhammad Torequl Islam  1 , William C Cho  4 , Miquel Martorell  5 , Javad Sharifi-Rad  6 , Monica Butnariu  7 , Almagul Umbetova  8 , Daniela Calina  9
Affiliations

Natural Compounds or Their Derivatives against Breast Cancer: A Computational Study

Rajib Hossain et al. Biomed Res Int. .

Abstract

Background: Breast cancer is one of the most common types of cancer diagnosed and the second leading cause of death among women. Breast cancer susceptibility proteins of type 1 and 2 are human tumor suppressor genes. Genetic variations/mutations in these two genes lead to overexpression of human breast tumor suppressor genes (e.g., BRCA1, BRCA2), which triggers uncontrolled duplication of cells in humans. In addition, multidrug resistance protein 1 (MDR1), an important cell membrane protein that pumps many foreign substances from cells, is also responsible for developing resistance to cancer chemotherapy. Aim of the Study. The aim of this study was to analyze some natural compounds or their derivatives as part of the development of strong inhibitors for breast cancer. Methodology. Molecular docking studies were performed using compounds known in the literature to be effective against BRCA1 and BRCA2 and MDR1, with positive control being 5-fluorouracil, an antineoplastic drug as a positive control.

Results: The binding affinity of the compounds was analyzed, and it was observed that they had a better binding affinity for the target proteins than the standard drug 5-fluorouracil. Among the compounds analyzed, α-hederin, andrographolide, apigenin, asiatic acid, auricular acid, sinularin, curcumin, citrinin, hispolon, nerol, phytol, retinol palmitate, and sclareol showed the best binding affinity energy to the BRCA1, BRCA2, and MDR1 proteins, respectively.

Conclusions: α-Hederin, andrographolide, apigenin, asiatic acid, auricular acid, hispolon, sclareol, curcumin, citrinin, and sinularin or their derivatives can be a good source of anticancer agents in breast cancer.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The chemical structure of the screened compounds.
Figure 2
Figure 2
The three-dimensional structure of (a) BRCA1 (4Y2G), (b) BRCA2 (3EU7), and (c) MDR1 (6C0V).
Figure 3
Figure 3
The four best docking results for the best screened compounds with BRCA1 (PDB: 4Y2G) protein.
Figure 4
Figure 4
Docking results for the four best screened compounds with BRCA2 (3EU7) protein.
Figure 5
Figure 5
The four best docking results for screened compounds with MDR1 (6C0V) protein.
See this image and copyright information in PMC

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