IN SILICO ASSESSMENT OF SOME BIOACTIVE MARINE XANTHONE DERIVATIVES AS POTENT INHIBITORS OF PI3Kγ BY MOLECULAR DOCKING APPROACH

Cao Hồng Lê; Nguyễn Ngọc Thụy; Trương Thị Thùy Nhung; Bùi Thị Thực; Mạc Thị Nguyên; Nguyễn Trung Đức; Đậu Đình Khải; Đinh Thị Thùy Linh; Nguyễn Lan Hương

doi:10.34238/tnu-jst.9680

IN SILICO ASSESSMENT OF SOME BIOACTIVE MARINE XANTHONE DERIVATIVES AS POTENT INHIBITORS OF PI3Kγ BY MOLECULAR DOCKING APPROACH

About this article

Received: 05/02/24 Revised: 29/02/24 Published: 29/02/24

Authors

1. Cao Hong Le , TNU - University of Agriculture and Forestry
2. Nguyen Ngoc Thuy, Ho Chi Minh City University of Industry and Trade
3. Truong Thi Thuy Nhung, Phenikaa University
4. Bui Thi Thuc, Institude of Natural Products Chemistry- Vietnam Academy of Science and Technology
5. Mac Thi Nguyen, Sao Do University
6. Nguyen Trung Duc, Hanoi National University of Education
7. Dau Dinh Khai, Hanoi National University of Education
8. Dinh Thi Thuy Linh, Hanoi National University of Education
9. Nguyen Lan Huong, Hanoi National University of Education

Abstract

Protein PI3Kγ is a well-defined kinase target for cancer treatment that is important in regulating cell signaling, metabolism, growth, and cell proliferation. Our research aims to assess the anti-proliferation activity and mechanisms, the dual PI3K/mTOR binding affinity, and the mechanism of action of a series of bioactive xanthone derivatives from the marine. The performance of the AutoDock Vina software for predicting ligand-receptor binding affinities and poses of the compounds under study was first verified by available experimental data. Based on the validated AutoDock Vina parameters, a database of 169 marine xanthones were screened against the protein PI3Kγ. Natural compounds with lower docking scores (ΔG = -9,12 kcal/mol) than the positive control were subjected to MD simulation to evaluate structural changes compliant with the protein PI3Kγ. Structure and energy analyses showed that Austocystin L is highly stable within the active sites of the protein PI3Kγ. Austocystin L and Neocitreamicins I were suggested as agents against the protein PI3Kγ and to direct further biochemical experiments based on in silico calculations.

Keywords

Protein PI3Kγ; Marine xanthones; AutoDock Vina parameters; Austocystin L; Neocitreamicins I

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DOI: https://doi.org/10.34238/tnu-jst.9680

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