MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer's Disease

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2023 Dec 23

PMID 38139780

Authors

Rodrigo Mancini Santos

Camila Assis Tavares

Tainah Martins Resende Santos

Hassan Rasouli

Teodorico Castro Ramalho

Affiliations

Soon will be listed here.

Abstract

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)]·HO (VC1) and [VO(bpy)Cl] (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + HO (1), VC2 + HO (2), VC1 + AMPK + HO (3), and VC2 + ULK1 + HO (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with , a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + HO. Nevertheless, for the system VC2 + ULK1 + HO, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.

References

Ospina-Romero M, Glymour M, Hayes-Larson E, Mayeda E, Graff R, Brenowitz W . Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020; 3(11):e2025515. PMC: 7666424. DOI: 10.1001/jamanetworkopen.2020.25515. View

Mustafi D, Peng B, Foxley S, Makinen M, Karczmar G, Zamora M . New vanadium-based magnetic resonance imaging probes: clinical potential for early detection of cancer. J Biol Inorg Chem. 2009; 14(8):1187-97. DOI: 10.1007/s00775-009-0562-0. View

Rajasekhar K, Govindaraju T . Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease. RSC Adv. 2022; 8(42):23780-23804. PMC: 9081849. DOI: 10.1039/c8ra03620a. View

Villa A, Stock G . What NMR Relaxation Can Tell Us about the Internal Motion of an RNA Hairpin: A Molecular Dynamics Simulation Study. J Chem Theory Comput. 2015; 2(5):1228-36. DOI: 10.1021/ct600160z. View

Thabah D, Syiem D, Pakyntein C, Banerjee S, Kharshiing C, Bhattacharjee A . upregulate GLUT4, AMPK, AKT and insulin in alloxan-induced diabetic mice: an in vivo and in silico study. Arch Physiol Biochem. 2021; 129(5):1071-1083. DOI: 10.1080/13813455.2021.1897145. View

Gupta A, Caravan P, Price W, Platas-Iglesias C, Gale E . Applications for Transition-Metal Chemistry in Contrast-Enhanced Magnetic Resonance Imaging. Inorg Chem. 2020; 59(10):6648-6678. PMC: 8047401. DOI: 10.1021/acs.inorgchem.0c00510. View

Kruger G, Kastrup A, Glover G . Neuroimaging at 1.5 T and 3.0 T: comparison of oxygenation-sensitive magnetic resonance imaging. Magn Reson Med. 2001; 45(4):595-604. DOI: 10.1002/mrm.1081. View

Porsteinsson A, Isaacson R, Knox S, Sabbagh M, Rubino I . Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021. J Prev Alzheimers Dis. 2021; 8(3):371-386. DOI: 10.14283/jpad.2021.23. View

Giacoppo J, Franca T, Kuca K, da Cunha E, Abagyan R, Mancini D . Molecular modeling and in vitro reactivation study between the oxime BI-6 and acetylcholinesterase inhibited by different nerve agents. J Biomol Struct Dyn. 2014; 33(9):2048-58. DOI: 10.1080/07391102.2014.989408. View

10.

Deoni S . Quantitative relaxometry of the brain. Top Magn Reson Imaging. 2011; 21(2):101-13. PMC: 3613135. DOI: 10.1097/RMR.0b013e31821e56d8. View

11.

Semiz S . Vanadium as potential therapeutic agent for COVID-19: A focus on its antiviral, antiinflamatory, and antihyperglycemic effects. J Trace Elem Med Biol. 2021; 69:126887. PMC: 8555110. DOI: 10.1016/j.jtemb.2021.126887. View

12.

Fitzgerald R, Antoniou A, Fruk L, Rosenfeld N . The future of early cancer detection. Nat Med. 2022; 28(4):666-677. DOI: 10.1038/s41591-022-01746-x. View

13.

Dong Y, Stewart T, Zhang Y, Shi M, Tan C, Li X . Anti-diabetic vanadyl complexes reduced Alzheimer's disease pathology independent of amyloid plaque deposition. Sci China Life Sci. 2018; 62(1):126-139. DOI: 10.1007/s11427-018-9350-1. View

14.

Zablocka A, Kazana W, Sochocka M, Stanczykiewicz B, Janusz M, Leszek J . Inverse Correlation Between Alzheimer's Disease and Cancer: Short Overview. Mol Neurobiol. 2021; 58(12):6335-6349. PMC: 8639554. DOI: 10.1007/s12035-021-02544-1. View

15.

Zhang L, Sanagapalli S, Stoita A . Challenges in diagnosis of pancreatic cancer. World J Gastroenterol. 2018; 24(19):2047-2060. PMC: 5960811. DOI: 10.3748/wjg.v24.i19.2047. View

16.

Paquet C, de Haan H, Leek D, Lin H, Xiang B, Tian G . Clusters of superparamagnetic iron oxide nanoparticles encapsulated in a hydrogel: a particle architecture generating a synergistic enhancement of the T2 relaxation. ACS Nano. 2011; 5(4):3104-12. DOI: 10.1021/nn2002272. View

17.

Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H . Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 2005; 40(11):715-24. DOI: 10.1097/01.rli.0000184756.66360.d3. View

18.

Goncalves M, Goncalves A, Franca T, Santana M, da Cunha E, Ramalho T . Improved Protocol for the Selection of Structures from Molecular Dynamics of Organic Systems in Solution: The Value of Investigating Different Wavelet Families. J Chem Theory Comput. 2022; 18(10):5810-5818. DOI: 10.1021/acs.jctc.2c00593. View

19.

Pessoa J, Etcheverry S, Gambino D . Vanadium compounds in medicine. Coord Chem Rev. 2020; 301:24-48. PMC: 7094629. DOI: 10.1016/j.ccr.2014.12.002. View

20.

Lazarus M, Novotny C, Shokat K . Structure of the human autophagy initiating kinase ULK1 in complex with potent inhibitors. ACS Chem Biol. 2015; 10(1):257-61. PMC: 4301081. DOI: 10.1021/cb500835z. View