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- Title
Potential JAK2 Inhibitors from Selected Natural Compounds: A Promising Approach for Complementary Therapy in Cancer Patients.
- Authors
Vaziri-Amjad, Samaneh; Rahgosha, Reza; Taherkhani, Amir
- Abstract
Background. Janus-activated kinase 2 (JAK2) plays a pivotal role in numerous essential biological processes, including proliferation, apoptosis, and metastasis in human cells. Prior studies have indicated that inhibiting JAK2 could be a promising strategy to mitigate cell proliferation and induce apoptosis in tumor cells. Objectives. This study aimed to estimate the binding affinity of 79 herbal compounds, comprising 46 flavonoids, 21 anthraquinones, and 12 cinnamic acids, to the ATP-binding cleft of JAK2 to identify potential herbal inhibitors of JAK2. Methods. The binding affinities between ligands and JAK2 were calculated utilizing AutoDock 4.0 software in conjunction with the Cygwin environment. Cross-validation was conducted using the Schrödinger tool. Molecular dynamics simulations were employed to evaluate the stability of docked poses for the most significant JAK2 inhibitors. Furthermore, the Discovery Studio Visualizer tool was utilized to elucidate interactions between the top-ranked JAK2 inhibitors and residues within the JAK2 ATP-binding site. Results. Twelve flavonoids, two anthraquinones, and three cinnamic acids demonstrated substantial binding affinities to the protein kinase domain of the receptor, with a criterion of Δ G binding < −10 kcal/mol. Among the studied flavonoids, anthraquinones, and cinnamic acid derivatives, orientin, chlorogenic acid, and pulmatin emerged as the most potent JAK2 inhibitors, exhibiting Δ G binding scores of −14.49, −11.87, and −10.76 kcal/mol, respectively. Furthermore, the docked poses of orientin, pulmatin, and chlorogenic acid remained stable throughout 60 ns computer simulations. The average root mean square deviation values calculated for JAK2 when complexed with orientin, chlorogenic acid, and pulmatin were 2.04 Å, 2.06 Å, and 1.95 Å, respectively. Conclusion. This study underscores the robust inhibitory potential of orientin, pulmatin, and chlorogenic acid against JAK2. The findings hold promise for the development of novel and effective drugs for cancer treatment.
- Subjects
PHYTOTHERAPY; THERAPEUTIC use of antineoplastic agents; COMPUTER simulation; LIGANDS (Chemistry); FLAVONOIDS; QUINONE; CELL proliferation; APOPTOSIS; CANCER patients; PHYTOCHEMICALS; PLANT extracts; CARBOCYCLIC acids; JANUS kinases; ALTERNATIVE medicine; MOLECULAR structure; RESEARCH methodology; NEUROTRANSMITTER uptake inhibitors; TUMORS; DATA analysis software
- Publication
Evidence-based Complementary & Alternative Medicine (eCAM), 2024, Vol 2024, p1
- ISSN
1741-427X
- Publication type
Article
- DOI
10.1155/2024/1114928