Computational study of naphthylisoquinoline alkaloids with antimalarial activity from Dioncophyllaceae and Ancistrodaceae in vacuo

Mammino, Liliana; Bilonda, Mireille K.

doi:10.1007/s00214-016-1843-7

Cited by 10 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dipolar momentum is associated with compounds having unsymmetrical electronic density, thus, higher dipolar momentum favors dipole-dipole, cation-π or π-π interactions (Sharma and Rastogi 2007; Lien 1982). In this respect, this result could support the previous experimental investigations, which suggested that antimalarial activity is related to the inhibition of cytochrome bc1, which is highly influenced by the hydrogen bond formation between leucine, histidine and glutamate present in cytochrome bc1 with ligand as atovaquone and clopidol derivatives [24,25,26,27,28,29].…”

Section: Resultssupporting

confidence: 89%

Classical QSAR and Docking Simulation of 4-Pyridone Derivatives for Their Antimalarial Activity

et al. 2018

View full text Add to dashboard Cite

In this work, the minimum energy structures of 22 4-pyridone derivatives have been optimized at Density Functional Theory level, and several quantum molecular, including electronic and thermodynamic descriptors, were computed for these substrates in order to obtain a statistical and meaningful QSAR equation. In this sense, by using multiple linear regressions, five mathematical models have been obtained. The best model with only four descriptors (r2 = 0.86, Q2 = 0.92, S.E.P = 0.38) was validated by the leave-one-out cross-validation method. The antimalarial activity can be explained by the combination of the four mentioned descriptors e.g., electronic potential, dipolar momentum, partition coefficient and molar refractivity. The statistical parameters of this model suggest that it is robust enough to predict the antimalarial activity of new possible compounds; consequently, three small chemical modifications into the structural core of these compounds were performed specifically on the most active compound of the series (compound 13). These three new suggested compounds were leveled as 13A, 13B and 13C, and the predicted biological antimalarial activity is 0.02 µM, 0.03 µM, and 0.07 µM, respectively. In order to complement these results focused on the possible action mechanism of the substrates, a docking simulation was included for these new structures as well as for the compound 13 and the docking scores (binding affinity) obtained for the interaction of these substrates with the cytochrome bc1, were −7.5, −7.2, −6.9 and −7.5 kcal/mol for 13A, 13B, 13C and compound 13, respectively, which suggests that these compounds are good candidates for its biological application in this illness.

show abstract

Section: Resultssupporting

confidence: 89%

Classical QSAR and Docking Simulation of 4-Pyridone Derivatives for Their Antimalarial Activity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The HF method is a common and less expensive quantum method that can yield accurate information regarding conformational analysis. HF can handle intramolecular hydrogen bonding, as shown in previous studies of other molecules [ 18 , 19 , 20 , 21 ]. DFT is an alternative method to wavefunction approaches, which is often used in a conformational search because it takes into account part of the correlation effects at a comparatively low cost.…”

Section: Computational Detailsmentioning

confidence: 73%

Intramolecular Hydrogen Bonds in Conformers of Quinine and Quinidine: An HF, MP2 and DFT Study

Bilonda

Mammino

2017

Molecules

Self Cite

View full text Add to dashboard Cite

Quinine is an alkaloid with powerful antimalarial activity, isolated from the bark of Peru’s cinchona trees. Quinidine is an erythro diastereoisomer of quinine also exhibiting antimalarial activity. Conformational studies performed so far had never identified conformers with intramolecular hydrogen bonds (IHB). The current study shows the possibility of conformers with an IHB between the quinuclidine and quinoline moieties of these molecules. The study was performed at different levels of theory: Hartree Fock (HF) with the 6-31G(d,p) basis set, Density Functional Theory (DFT) with the B3LYP functional and the 6-31+G(d,p) basis set and Møller–Plesset Perturbation Theory (MP2) with the 6-31+G(d,p) basis set, to confirm the results. The results suggest that the stabilising effect of this IHB is weaker or comparable with respect to the stabilising effect of the preferred mutual orientation of the two moieties. Although the IHB-containing conformers may not be the lowest energy ones, their relative energy is sufficiently low for them to be included among the possible ones responsible for the compounds’ antimalarial activity.

show abstract

Computational Study of Shuangancistrotectorine A: A Naphthylisoquinoline Alkaloid with Antimalarial Activity

Bilonda

Mammino

2020

Advances in Quantum Systems in Chemistry, Physics, and Biology

View full text Add to dashboard Cite

Computational study of naphthylisoquinoline alkaloids with antimalarial activity from Dioncophyllaceae and Ancistrodaceae in vacuo

Cited by 10 publications

References 49 publications

Classical QSAR and Docking Simulation of 4-Pyridone Derivatives for Their Antimalarial Activity

Classical QSAR and Docking Simulation of 4-Pyridone Derivatives for Their Antimalarial Activity

Intramolecular Hydrogen Bonds in Conformers of Quinine and Quinidine: An HF, MP2 and DFT Study

Computational Study of Shuangancistrotectorine A: A Naphthylisoquinoline Alkaloid with Antimalarial Activity

Contact Info

Product

Resources

About