Exploring the potential of phytochemicals as inhibitors of 3'-phosphoadenosine 5'-phosphosulfate synthase 1 targeting cancer therapy

被引:0
作者
Alharbi, Bandar [1 ]
Alharethi, Salem Hussain [2 ]
Abu Al-Soud, Waleed [3 ]
Al-Keridis, Lamya Ahmed [4 ]
Aljohani, Abdullah A. [5 ]
Jairajpuri, Deeba Shamim [6 ]
Alshammari, Nawaf [7 ]
Adnan, Mohd [7 ,8 ]
机构
[1] Univ Hail, Coll Appl Med Sci, Dept Med Lab Sci, Hail, Saudi Arabia
[2] Najran Univ, Coll Arts & Sci, Dept Biol Sci, Najran, Saudi Arabia
[3] Jouf Univ, Fac Appl Med Sci, Dept Clin Lab Sci, Sakaka, Saudi Arabia
[4] Princess Nourah Bint Abdulrahman Univ, Coll Sci, Dept Biol, Riyadh, Saudi Arabia
[5] Jouf Univ, Coll Appl Med Sci Qurayyat, Dept Clin Lab Sci, Sakaka, Saudi Arabia
[6] Arabian Gulf Univ, Coll Med & Med Sci, Dept Med Biochem, Manama, Bahrain
[7] Univ Hail, Coll Sci, Dept Biol, Hail, Saudi Arabia
[8] Univ Hail, Coll Sci, Dept Biol, POB 2440, Hail, Saudi Arabia
关键词
3'-phosphoadenosine 5'-phosphosulfate synthase; phytochemicals; drug discovery; non-small cell lung cancer; virtual screening; molecular docking; MOLECULAR-DYNAMICS SIMULATION; CELL LUNG-CANCER; IDENTIFICATION; MECHANISM; INSIGHTS; BIOLOGY;
D O I
10.1080/07391102.2023.2212810
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is an enzyme that critically synthesises the biologically active form of sulfate (PAPS) for all sulfation reactions. The discovery of PAPSS1 as a possible drug target for cancer therapy, specifically in non-small cell lung cancer, has prompted us to investigate potential small-molecule inhibitors of PAPSS1. Here, a structure-based virtual screening method was used to search for phytochemicals in the IMPPAT database to find potential inhibitors of PAPSS1. The primary hits were selected based on their physicochemical, ADMET, and drug-like properties. Then, the binding affinities were calculated and analyzed the interactions to identify safer and more effective hits. The research identified two phytochemicals, Guggulsterone and Corylin, that exhibited significant affinity and specific interaction with the ATP-binding pocket of PAPSS1. Structural observations made by molecular docking were further accompanied by molecular dynamics (MD) simulations and principal component analysis (PCA) to examine the conformational changes and stability of PAPSS1 with the elucidated compounds Guggulsterone and Corylin. MD simulation results suggested that the binding of Guggulsterone and Corylin stabilizes the PAPSS1 structure, leading to fewer conformational changes. This implies that these compounds may be useful in developing PAPSS1 inhibitors for the therapeutic development against non-small cell lung cancer (NSCLC). This study highlights the potential of phytochemicals as PAPSS1 inhibitors and the utility of computational approaches in drug discovery.Communicated by Ramaswamy H. Sarma
引用
收藏
页码:3193 / 3203
页数:11
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