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Innovative Medicines & Omics Femtomolar inhibition of pseudoeriocitrin

oxygen radicals are highly reactive and can trigger a compared to other molecules. The oxygen atoms within
contagious radical attack. In this study, we discovered these structures facilitate the formation of hydrogen bonds,
that molecules with a high abundance of oxygen radicals hence positively affecting binding affinity. Ligands featuring
can form multiple hydrogen bonds. The geometry of a wide tetracyclic core structure tend to be more effectively
the molecule also plays a significant role in this process. accommodated in protein binding sites compared to those
However, reducing molecules will transform these radicals lacking a tetracyclic core structure. Furthermore, these
into more stable molecules. In contrast, when there are molecules showed promising selectivity. They inhibited the
high levels of oxygen radicals within a molecule – as seen enzymes in target parasites without significantly affecting
in pseudoeriocitrin, for example – this neutralization can human homologs of the same enzyme or did so with lower
take considerably longer than other radical molecules. affinity.
Non-radical oxygen, on the other hand, cannot position Previous studies have demonstrated the connection
themselves in such geometries because the atom is unable between the structural, electronic, topological,
to accommodate additional oxygen if it is already double- and vibrational properties of the synthesized
bonded to carbon. The most significant advantage of this 4-methylbenzylammonium nitrate (4MBN) and its
radical molecule is its potential for femtomolar inhibition, non-covalent interactions using the combination of
suggesting that it may be useful for further investigation, B3LYP/CC-PVTZ calculations and molecular docking
especially in vitro, for cancer research. When examining techniques. The results suggest that 4MBN exhibits
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the structure of anticancer drugs, such as bleomycin, we biological activity and could serve as a potential inhibitor
cannot help but wonder why such a multiradical should against schizophrenia.
not be explored for use against solid tumors.
To synthesize a pseudoeriocitrin-like molecule, one
The molecular structures, HOMO-LUMO energy, could propose a reaction where eriocitrin is oxidized (e.g.,
electronic property, reactivity, and MEP of the main catalyzed by high temperature and metal), leading to bond
components in the essential oil of Phlomis bruguieri formation between C3 and C8, resulting in a tetracyclic
Desf. were analyzed in a previous study. The study planar core structure. Given that pseudoeriocitrin
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focused on the most abundant molecules present in the may exist only briefly in a biological environment,
essential oil, which include caryophyllene oxide, β-pinene, various characterization techniques can confirm its
1,8-cineole, α-cubene, and β-caryophyllene molecules, to existence and activity. In an experimental study by
evaluate their interactions with water through theoretical Gatfaoui et al., single crystals of a new proton transfer
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calculations. In all examined molecules, the electrostatic compound, phenylethylammonium trioxonitrate, were
potential was predominantly determined by the oxygen analyzed by solid-state XRD, thermal analysis, Infrared
atoms, which serve as reactive sites for electrophilic attack. IR spectroscopy, and ionic conductivity to identify the
For β-caryophyllene, caryophyllene oxide, and 1,8-cineole, chemical structure of the newly synthesized ligand. XRD
the introduction of a water molecule increased the size of revealed a slotted behavior of NO anions at the y = 1/4
−
3
the energy gap. This suggests that adding water to these and 3/4 positions, where 2-phenylethylammonium groups
systems slightly altered the energy gap values of the studied are linked by CeH/p interactions. The study evaluated the
substances. Similarly, the introduction of water into results from XRD analysis and MEP to obtain electron
eriocitrin may affect its energy gap and stability. Therefore, density maps of the ligand and accurately predicted its
it would be beneficial to investigate this assumption using chemical structure and interactions. If pseudoeriocitrin,
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the methodology outlined in the study by Akman et al. 32 the virtual compound examined in the present study,
Planar molecular geometry and the presence of can be synthesized, it could be analyzed using XRD after
electron-rich oxygen atoms offer significant benefits for crystallization. Its existence may also be investigated by
ligands when fitting into protein cavities and interacting HPLC without crystallization, and its structure analyzed
with surrounding residues. The multi-ring core structure using NMR.
of planar geometry occupies a large area, enhancing the
possibility of surrounding residues approaching the ligand 4. Conclusion
from all directions. In our previous studies on the inhibitory Pseudoeriocitrin demonstrates a remarkable ability to
capabilities of various plant secondary metabolites, we inhibit various enzymes at extremely low concentrations
4,33
observed similar trends during protein docking analyses. without forming covalent bonds. Even if covalent bonds
Compounds such as cucurbitacin-B, momordicin-II, are formed, they only last for a short duration. Therefore,
and charantadiol-A, which possess steroidal centers and it is essential to continue this investigation to validate the
various oxygen atoms, exhibit stronger inhibition potential efficacy and safety of pseudoeriocitrin. Further investigation

Volume 2 Issue 2 (2025) 92 doi: 10.36922/imo.6026