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In Silico Methods Applied in Drug and Pesticide Discovery, 2nd Edition

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Computational and Theoretical Chemistry".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2134

Special Issue Editors

Dr. Ana Borota

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Guest Editor
Coriolan Dragulescu Institute of Chemistry of the Romanian Academy, 24 M. Viteazu Avenue, 300223 Timisoara, Romania
Interests: theoretical chemistry; molecular modeling; homology modeling; molecular docking; ligand- and structure-based pharmacophores; virtual screening; conformational analyses; QSAR studies; medicinal chemistry; agrochemicals
Special Issues, Collections and Topics in MDPI journals
Dr. Simona Funar-Timofei

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Guest Editor
Coriolan Dragulescu Institute of Chemistry of the Romanian Academy, 24 M. Viteazu Avenue, 300223 Timisoara, Romania
Interests: molecular modeling; ligand-based design; agrochemicals; chemometrics; environmental chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nowadays, there is a successful large-scale application of computational techniques (in silico methods) in the area of drug discovery, while a smaller involvement of these techniques has been noted in the field of agrochemistry. In silico methods are especially applied in the early stages of the research process, when basic studies aim to decipher the biology associated with the desired pharmacological/agrochemical response, prioritizing drug/pesticide targets, and identifying or optimizing new active chemical entities. The great advantages of computational methods consist of rapidity and cost-effectiveness compared with in vitro/vivo tests.

Dr. Ana Borota
Dr. Simona Funar-Timofei
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular modeling of small and complex molecules/macromolecules
  • homology modeling
  • molecular docking
  • virtual screening
  • ADME-tox
  • ligand- and structure-based pharmacophore modeling
  • QSAR/QSPR models
  • drug/pesticide design

Related Special Issue

Published Papers (3 papers)

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Research

20 pages, 6018 KiB  
Article
Investigation of the Anti-Inflammatory Properties of Bioactive Compounds from Olea europaea: In Silico Evaluation of Cyclooxygenase Enzyme Inhibition and Pharmacokinetic Profiling
by Tom C. Karagiannis, Katherine Ververis, Julia J. Liang, Eleni Pitsillou, Evan A. Kagarakis, Debbie T. Z. Yi, Vivian Xu, Andrew Hung and Assam El-Osta
Molecules 2024, 29(15), 3502; https://doi.org/10.3390/molecules29153502 - 26 Jul 2024
Abstract
In a landmark study, oleocanthal (OLC), a major phenolic in extra virgin olive oil (EVOO), was found to possess anti-inflammatory activity similar to ibuprofen, involving inhibition of cyclooxygenase (COX) enzymes. EVOO is a rich source of bioactive compounds including fatty acids and phenolics; [...] Read more.
In a landmark study, oleocanthal (OLC), a major phenolic in extra virgin olive oil (EVOO), was found to possess anti-inflammatory activity similar to ibuprofen, involving inhibition of cyclooxygenase (COX) enzymes. EVOO is a rich source of bioactive compounds including fatty acids and phenolics; however, the biological activities of only a small subset of compounds associated with Olea europaea have been explored. Here, the OliveNetTM library (consisting of over 600 compounds) was utilized to investigate olive-derived compounds as potential modulators of the arachidonic acid pathway. Our first aim was to perform enzymatic assays to evaluate the inhibitory activity of a selection of phenolic compounds and fatty acids against COX isoforms (COX-1 and COX-2) and 15-lipoxygenase (15-LOX). Olive compounds were found to inhibit COX isoforms, with minimal activity against 15-LOX. Subsequent molecular docking indicated that the olive compounds possess strong binding affinities for the active site of COX isoforms, and molecular dynamics (MD) simulations confirmed the stability of binding. Moreover, olive compounds were predicted to have favorable pharmacokinetic properties, including a readiness to cross biological membranes as highlighted by steered MD simulations and umbrella sampling. Importantly, olive compounds including OLC were identified as non-inhibitors of the human ether-à-go-go-related gene (hERG) channel based on patch clamp assays. Overall, this study extends our understanding of the bioactivity of Olea-europaea-derived compounds, many of which are now known to be, at least in part, accountable for the beneficial health effects of the Mediterranean diet. Full article
(This article belongs to the Special Issue In Silico Methods Applied in Drug and Pesticide Discovery, 2nd Edition)
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25 pages, 5186 KiB  
Article
Kinetic Study and Reaction Mechanism of the Gas-Phase Thermolysis Reaction of Methyl Derivatives of 1,2,4,5-Tetroxane
by Alexander G. Bordón, Mariela I. Profeta, Jorge M. Romero, María J. Jorge, Lilian C. Jorge, Nelly L. Jorge, C. Ignacio Sainz-Díaz, Juliana Cuéllar-Zuquin, Daniel Roca-Sanjuán, César Viseras Iborra, André Grand and Alfonso Hernández-Laguna
Molecules 2024, 29(14), 3274; https://doi.org/10.3390/molecules29143274 - 11 Jul 2024
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Abstract
Tetroxane derivatives are interesting drugs for antileishmaniasis and antimalaric treatments. The gas-phase thermal decomposition of 3,6,-dimethyl-1,2,4,5-tetroxane (DMT) and 3,3,6,6,-tetramethyl-1,2,4,5-tetroxane (acetone diperoxide (ACDP)) was studied at 493–543 K by direct gas chromatography by means of a flow reactor. The reaction is produced in the [...] Read more.
Tetroxane derivatives are interesting drugs for antileishmaniasis and antimalaric treatments. The gas-phase thermal decomposition of 3,6,-dimethyl-1,2,4,5-tetroxane (DMT) and 3,3,6,6,-tetramethyl-1,2,4,5-tetroxane (acetone diperoxide (ACDP)) was studied at 493–543 K by direct gas chromatography by means of a flow reactor. The reaction is produced in the injector chamber at different temperatures. The resulting kinetics Arrhenius equations were calculated for both tetroxanes. Including the parent compound of the series 1,2,4,5-tetroxane (formaldehyde diperoxide (FDP)), the activation energy and frequency factors decrease linearly with the number of methyl groups. The reaction mechanisms of ACDP and 3,6,6-trimethyl-1,2,4,5-tetroxane (TMT) decomposition have been studied by means of the DFT method with the BHANDHLYP functional. Our calculations confirm that the concerted mechanism should be discarded and that only the stepwise mechanism occurs. The critical points of the singlet and triplet state potential energy surfaces (S- and T-PES) of the thermolysis reaction of both compounds have been determined. The calculated activation energies of the different steps vary linearly with the number of methyl groups of the methyl-tetroxanes series. The mechanism for the S-PES leads to a diradical O···O open structure, which leads to a C···O dissociation in the second step and the production of the first acetaldehyde/acetone molecule. This last one yields a second C···O dissociation, producing O2 and another acetone/acetaldehyde molecule. The O2 molecule is in the singlet state. A quasi-parallel mechanism for the T-PES from the open diradical to products is also found. Most of the critical points of both PES are linear with the number of methyl groups. Reaction in the triplet state is much more exothermic than the singlet state mechanism. Transitions from the singlet ground state, S0 and low-lying singlet states S1–3, to the low-lying triplet excited states, T1–4, (chemical excitation) in the family of methyl tetroxanes are also studied at the CASSCF/CASPT2 level. Two possible mechanisms are possible here: (i) from S0 to T3 by strong spin orbit coupling (SOC) and subsequent fast internal conversion to the excited T1 state and (ii) from S0 to S2 from internal conversion and subsequent S2 to T1 by SOC. From these experimental and theoretical results, the additivity effect of the methyl groups in the thermolysis reaction of the methyl tetroxane derivatives is clearly highlighted. This information will have a great impact for controlling these processes in the laboratory and chemical industries. Full article
(This article belongs to the Special Issue In Silico Methods Applied in Drug and Pesticide Discovery, 2nd Edition)
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21 pages, 3862 KiB  
Article
Identification and Evaluation of Olive Phenolics in the Context of Amine Oxidase Enzyme Inhibition and Depression: In Silico Modelling and In Vitro Validation
by Tom C. Karagiannis, Katherine Ververis, Julia J. Liang, Eleni Pitsillou, Siyao Liu, Sarah M. Bresnehan, Vivian Xu, Stevano J. Wijoyo, Xiaofei Duan, Ken Ng, Andrew Hung, Erik Goebel and Assam El-Osta
Molecules 2024, 29(11), 2446; https://doi.org/10.3390/molecules29112446 - 23 May 2024
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Abstract
The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea [...] Read more.
The Mediterranean diet well known for its beneficial health effects, including mood enhancement, is characterised by the relatively high consumption of extra virgin olive oil (EVOO), which is rich in bioactive phenolic compounds. Over 200 phenolic compounds have been associated with Olea europaea, and of these, only a relatively small fraction have been characterised. Utilising the OliveNetTM library, phenolic compounds were investigated as potential inhibitors of the epigenetic modifier lysine-specific demethylase 1 (LSD1). Furthermore, the compounds were screened for inhibition of the structurally similar monoamine oxidases (MAOs) which are directly implicated in the pathophysiology of depression. Molecular docking highlighted that olive phenolics interact with the active site of LSD1 and MAOs. Protein–peptide docking was also performed to evaluate the interaction of the histone H3 peptide with LSD1, in the presence of ligands bound to the substrate-binding cavity. To validate the in silico studies, the inhibitory activity of phenolic compounds was compared to the clinically approved inhibitor tranylcypromine. Our findings indicate that olive phenolics inhibit LSD1 and the MAOs in vitro. Using a cell culture model system with corticosteroid-stimulated human BJ fibroblast cells, the results demonstrate the attenuation of dexamethasone- and hydrocortisone-induced MAO activity by phenolic compounds. The findings were further corroborated using human embryonic stem cell (hESC)-derived neurons stimulated with all-trans retinoic acid. Overall, the results indicate the inhibition of flavin adenine dinucleotide (FAD)-dependent amine oxidases by olive phenolics. More generally, our findings further support at least a partial mechanism accounting for the antidepressant effects associated with EVOO and the Mediterranean diet. Full article
(This article belongs to the Special Issue In Silico Methods Applied in Drug and Pesticide Discovery, 2nd Edition)
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