Anti-Cancer Potency of Cucurbitacin D through PI3K and AKT1: A Molecular Docking Studies

DOI

10.2991/978-94-6463-431-0_2How to use a DOI?

Keywords

cucurbitacin D; cancer; AKT1; PI3K; docking

Abstract

Cucurbitacin is a bitter-tasting compound found in the Cucurbitaceae family. Previously, cucurbitacin D was observed to have antitumor activity in several tumor cell lines in vitro. Several macromolecules have been shown affected by cucurbitacin treatment, including AKT1, JAK, and STAT3. Nevertheless, molecular docking study to predict the direct target of this phytochemical agent is still very limited. Our research aims to investigate the interaction of cucurbitacin D to AKT1 and PI3K, which are recognized as prominent targets in cancer research. The crystal structures of PI3K and AKT were retrieved from the PDB database and further validated using Autodock. The 3D structure of cucurbitacin D was prepared and optimized using Avogadro software. Molecular docking was performed using Autodock, and the interactions were visualized using Biovia Discovery. Cucurbitacin D exhibited low binding energy when binding to AKT1 and PI3K, with values of -10.46 and -2.57 kcal/mol, respectively. Biovia Discovery simulations indicated that cucurbitacin D interacts with PI3K through two conventional hydrogen bonds, one alkyl and 1 Pi-alkyl bonds. Cucurbitacin D binds Lys833 within ATP-binding pocket of PI3K, through conventional hydrogen bond. Cucurbitacin D interacts with AKT1 through five conventional hydrogen bonds and four alkyl and two Pi-alkyl bonds. The Pi-alkyl interaction also involves Trp80 of PH domain. These results suggest that cucurbitacin D possesses anti-cancer potential by targeting PI3K and AKT.

Copyright

© 2024 The Author(s)

Open Access

Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial 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 license and indicate if changes were made.

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TY  - CONF
AU  - Nisa Yulianti Suprahman
AU  - Rohansyah Al-Bari
AU  - Refsya Azanti Putri
AU  - Muhammad Yogi Saputra
AU  - Sarmoko
PY  - 2024
DA  - 2024/05/30
TI  - Anti-Cancer Potency of Cucurbitacin D through PI3K and AKT1: A Molecular Docking Studies
BT  - Proceedings of selected papers of International Conference on Health, Science, and Environment (ICHSE 2023)
PB  - Atlantis Press
SP  - 4
EP  - 10
SN  - 2468-5747
UR  - https://doi.org/10.2991/978-94-6463-431-0_2
DO  - 10.2991/978-94-6463-431-0_2
ID  - Suprahman2024
ER  -