Design of N-11-Azaartemisinins Potentially Active against &amp;lt;i&amp;gt;Plasmodium falciparum&amp;lt;/i&amp;gt; by Combined Molecular Electrostatic Potential, Ligand-Receptor Interaction and Models Built with Supervised Machine Learning Methods

Castro, Jeferson Stiver Oliveira de; Pinheiro, José; Morais, Sílvia Simone dos Santos de; Bitencourt, Heriberto Rodrigues; Figueiredo, Antonio Florêncio de; Santos, Marcos Antonio Barros dos; Gil, Fábio dos Santos; Pinheiro, Ana Cecília Barbosa

doi:10.4236/jbpc.2023.141001

Cited by 1 publication

(1 citation statement)

References 57 publications

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“…The drug-receptor interaction (molecular docking) is a tool of choice when the threedimensional (3D) structure of the target protein is available (Stanzione et al, 2021;Araújo et al, 2023;Castro et al, 2023), and involves entropy and enthalpy effects, since the system with the highest entropy and lowest enthalpy is sought. Enthalpy is the energy content of a system and can be described by its variation (ΔH) (Vieira, 1999).…”

Section: Interaction Of Investigated Opioids With the Mormentioning

confidence: 99%

Scrutiny of Mitragynine and derivatives with analgesic potential using Mep and ligand-MOR interaction

Araújo,

Brito,

Pinheiro

et al. 2024

CLCS

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Mitragynine and derivatives with analgesic activity were scrutinized to unravel key structural features necessary for biological activities and interactions with the m-opioid receptor (MOR). Molecular electrostatic potential (MEP) scrutiny showed the anionic and phenolic sites, as well as the hydrophobic region of opioids, important for analgesic activity, susceptible to electrophilic attack by a biological target and that the presence of bulky substituents at C9 and C7 can hinder analgesia, through steric hindrance, and increase the positive MEP region in the phenolic site. Scrutiny of the interaction with the MOR showed the most active opioids, in general, having the tertiary N atom of the anionic site closest to the C atom from the COOH of the Asp147 residue of the MOR. Furthermore, opioids present hydrogen bond interactions between the H atom from the OCH3 of the phenolic site with the phenolic O atom from the OH of the Tyr148 residue of the MOR and of the H atom from the OH of this residue with the O atom from the OCH3 of the hydrophobic region. The accumulated insights led to the design of new derivatives and the identification of two (2) of them as promising derivatives for synthesis and biological assays.

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Section: Interaction Of Investigated Opioids With the Mormentioning

confidence: 99%