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2000
Volume 21, Issue 19
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Introduction

A mechanism has been proposed for the targeted transfer of an antimalarial drug, which involves 1, 2, and 4 trioxane (TRX) reagents. The trioxane ring is sensitive to ferrous iron, Fe(II), and when exposed to it, it breaks down into smaller pieces, releasing the antimalarial drug mML (a mock form of DPA1 inhibitor ML4118S).

Methods

The oxane ring is attached to a nanoparticle called adamantane, which helps facilitate the reaction. The mechanism has been investigated using two reactants: TRX-R-mML and TRX-H-mML complexes (R is a side chain). The researcher used the transition state theory, the Hartree-Fock level (HF), and the ground state series 6-31G** to investigate the mechanism. The physicochemical and geometric properties of the components involved in the reaction were measured to explain the mechanism better.

Results

The results indicate that the R as a side chain significantly affects the mentioned mechanism and properties. Additionally, the results of the calculations show the stability of the complexes required as reactants in the reaction.

Conclusion

The TRX-mML-R complex has more strength, and polarity than TRX-mML-H, and the energy level of the transition state of TRX-mML-R is lower than that of TRX-mML-H, indicating faster passage of raw materials.

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2024-10-01
2025-06-27
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References

  1. RayS. DasS. SuarM. Molecular Mechanism of Drug Resistance. Drug Resist. Bacteria, Fungi, Malaria.Cancer201720174711010.1007/978‑3‑319‑48683‑3_3
    [Google Scholar]
  2. RizviS.A.A. SalehA.M. Applications of nanoparticle systems in drug delivery technology.Saudi Pharm. J.2018261647010.1016/j.jsps.2017.10.012 29379334
    [Google Scholar]
  3. AdepuS. RamakrishnaS. Controlled drug delivery systems: Current status and future directions.Molecules20212619590510.3390/molecules26195905 34641447
    [Google Scholar]
  4. PandeyS.K. AnandU. SiddiquiW.A. TripathiR. Drug development strategies for malaria: With the hope for new antimalarial drug discovery—an update.Adv. Med.2023202311010.1155/2023/5060665 36960081
    [Google Scholar]
  5. National Center for Biotechnology InformationHeme B.2023Available From: https://pubchem.ncbi.nlm.nih.gov/compound/Heme-b
    [Google Scholar]
  6. RodriguesC.B. Validation of computational methods applied in molecular modeling of artemisinin with antimalarial activity.J. Computat. Theoret. Nanosci.201711955356110.1166/jctn.2014.3394
    [Google Scholar]
  7. DeuE. ChenI.T. LauterwasserE.M.W. ValderramosJ. LiH. EdgingtonL.E. RensloA.R. BogyoM. Ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo.Proc. Natl. Acad. Sci. USA201311045182441824910.1073/pnas.1312782110 24145449
    [Google Scholar]
  8. BayatZ. GholizadehA. Calculations of geometric parameters and physicochemical properties of complexes formed of FE(II)-reactive 1,2,4-trioxolane ring and some anti-malaria drugs via traceless linker.Pharm. Chem. J.201953541141810.1007/s11094‑019‑02012‑0
    [Google Scholar]
  9. BayatZ. Reyhani YassavoliA.R. The structure—bioresponse relationships studies of nucleoside derivatives conjugated with the 1-adamantane moiety.Russ. J. Phys. Chem. A. Focus Chem.201286221021410.1134/S0036024412020069
    [Google Scholar]
  10. AbbaspourN. HurrellR. KelishadiR. Review on iron and its importance for human health.J. Res. Med. Sci.2014192164174 24778671
    [Google Scholar]
  11. NemilovS.V. On the possibility of calculating entropy, free energy, and enthalpy of vitreous substances.Entropy (Basel)201820318710.3390/e20030187 33265278
    [Google Scholar]
  12. VoM.N. CallM. KowallC. JohnsonJ.K. Method for predicting dipole moments of complex molecules for use in thermophysical property estimation.Ind. Eng. Chem. Res.20195841192631927010.1021/acs.iecr.9b03699
    [Google Scholar]
  13. MaS. WangS. CaoJ. LiuF. Rapid and accurate estimation of activation free energy in hydrogen atom transfer-based C–H activation reactions: From empirical model to artificial neural networks.ACS Omega2022739348583486710.1021/acsomega.2c03252 36211072
    [Google Scholar]
  14. RajaeianE. Ab initio Study of Simple Mg-Ene Reactions of Propenyl Magnesium Halides and Ethylene (Type-1 Intermolecular Reaction).J. Phys. Theoret. Chem.20118119
    [Google Scholar]
  15. LaidlerK.J. KingM.C. Development of transition-state theory.J. Phys. Chem.198387152657266410.1021/j100238a002
    [Google Scholar]
  16. BernardinelliG. JeffordC.W. MaricD. ThomsonC. WeberJ. Computational studies of the structures and properties of potential antimalarial compounds based on the 1,2,4-trioxane ring structure. I. Artemisinin-like molecules.Int. J. Quantum Chem.199452S2111713110.1002/qua.560520710
    [Google Scholar]
  17. ThangarajR. FiserB. QiuX. LiC. ViskolczB. SzőriM. An ab initio investigation on relevant oligomerization reactions of Toluene Diisocyanate (TDI).Polymers (Basel)20221419418310.3390/polym14194183 36236129
    [Google Scholar]
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