Current Computer - Aided Drug Design - Volume 17, Issue 3, 2021
Volume 17, Issue 3, 2021
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Proton Hopping in Living Systems
More LessThis review focuses on the two-century-old concept of proton hopping. Introduced in 1806 by Grotthuss, it has evolved into an explanation of great diversity in describing many functions in living systems. It is a process involving water, which expands on the belief that life exists only in the presence of water. This review describes the mechanism of the process as it carries information through the water. A focus is initially made on the process of water in the nerve systems. The nature of the process in these systems is described as the passage of proton hopping in living systems. In drug-receptor encounters, proton hopping is initiated, carrying specific information from these specialized encounters. The review continues with an explanation of sleep, arising from an alteration in proton hopping. A similar phenomenon of the effect of general anesthetic agents is described, as they interfere with by proton hopping. Finally, memory functions are addressed in the realm of events carried by proton hopping.
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Anti-tumorigenic Efficacy of Tangeretin in Liver Cancer – An In Silico Approach
Authors: Sangavi P. and Langeswaran K.Background: Liver cancer is otherwise known as Hepatic cancer which originated from the liver. Hepatocellular carcinoma (HCC) is the common primary Liver cancer and is one of the emerging problems worldwide. Very few treatments are available to treat HCC because the molecular mechanism and other HCC mechanisms are still unclear. Cyclooxygenase 2 (COX-2), one of the most promising targets for Hepatocellular Carcinoma, is one of the dimeric enzymes which convert Arachidonic acid into Prostaglandin H2 in the step of Prostaglandin biosynthesis. Several natural bioactive compounds are involved in the treatment of various types of cancers. Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits, acts as an anti-oxidant modulator and anticancerous. Objectives: The main objective of this study is to find a suitable inhibitor for Hepatocellular Carcinoma. Methods: Computational approaches like molecular docking and molecular dynamics were performed to identify the potential inhibitor for Hepatocellular Carcinoma. Results: In this study, COX-2 was considered as a potential target for Hepatocellular Carcinoma which was examined with Tangeretin. Conclusion: Tangeretin was screened against C0X-2 which includes Molecular Docking, DFT analysis, ADMET prediction, and Molecular Dynamics simulation. Tangeretin had good docking scores, fulfilled the pharmacological properties through ADMET prediction, and the Protein-Ligand complex had good stability in Molecular Dynamics simulation.
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In Silico Discovery of Novel Flavonoids as Poly ADP Ribose Polymerase (PARP) Inhibitors
Authors: Ashish Shah, Ghanshyam Parmar and Avinash K. SethBackground: The concept of synthetic lethality is an emerging field in the treatment of cancer and can be applied for new drug development of cancer as already been represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. Objective: In this study, we performed virtual screening of 329 flavonoids obtained from the Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database to identify novel PARP inhibitors. Materials and Methods: Virtual screening carried out using different in silico methods which include molecular docking studies, prediction of drug-likeness and in silico toxicity studies. Results: Fifteen out of 329 flavonoids achieved better docking score as compared to rucaparib which is an FDA approved PARP inhibitor. These 15 hits were again rescored using accurate docking mode and drug-likeliness properties were evaluated. The accuracy of the docking method was checked using re-docking. Finally NPACT00183 and NPACT00280 were identified as potential PARP inhibitors with docking score of -139.237 and -129.36, respectively. These two flavonoids also showed no AMES toxicity and no carcinogenicity which was predicted using admetSAR. Conclusion: Our finding suggests that NPACT00183 and NPACT00280 have promising potential to be further explored as PARP inhibitors.
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Discovery of Novel Compounds Targeting DJ-1 as Neuroprotectants for Parkinson’s Disease by Virtual Screening and In Silico Method
Authors: Swati Sharan, Pravir Kumar and Rashmi K. AmbastaAim: To screen the zinc database for structurally similar molecules to compound 23 that targets DJ1 for use as a neuroprotective agent for Parkinson’s disease. Background: Parkinson’s disease (PD) is the second most common chronic neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra. To date, several proteins account for the recessive familial PD-forms, namely, Parkin, PINK-1, DJ-1, SNCA, PARK2, and LRRK2 Genes. DJ1 is one of the important central points that may be targeted for PD therapy. Recently, Compound 23 has been observed to exert the neuroprotective effect against neurodegeneration in a PD model, but due to its toxic substructure, the hunt for better nontoxic compounds continues. Objective: The overall objective of our work is to apply in silico approaches to screen structure similar compounds that interact potentially with DJ1 and may serve as a good therapeutic molecule for PD. Methods: Initial data mining was done from the zinc database and then screened compounds were additionally screened with toxicity checker, carcinopred, ADMET analysis and docking analysis. Results: The basic screening of database for structurally similar chemicals to compound 23 resulted in 50 compounds, which were further screened to twenty-three and finally seven compounds have been screened based on the toxicity and carcinopred test. Later, the seven compounds were docked and analysed for docking efficiency with DJ1. Our result of molecular docking and molecular simulation analysis highlights Molecule 42(SS2) to exhibit best binding affinity against DJ-1 protein target and can be proposed to be used as a therapeutic agent to modulate neurodegenerative proteins. Conclusion: Therefore, we conclude the discovery of novel, non-toxic, non-carcinogenic, ADMET investigated, capable of crossing BB barrier but structurally similar compounds to Compound-23, specifically molecule 42(SS2) and potentially molecule 34(SS1) to be used as neuroprotective agents for Parkinson’s disease.
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Lepidine B from Lepidium sativum Seeds as Multi-Functional Anti- Alzheimer’s Disease Agent: In Vitro and In Silico Studies
Authors: Serseg Talia, Khedidja Benarous, Meriem Lamrani and Mohamed YousfiObjective: The present study is carried out to screen the anticholinesterase effect of the total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B & E to inhibit AChE, BuChE, BACE, and MAGL. Hence, determining the main interactions in the inhibitorenzyme complex. Methods: Inhibitory effect of Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus extracts on acetylcholinesterase using the Ellman method was investigated with Donepezil as the positive control. A molecular docking study is achieved using Autodock Vina. The structures of target molecules Lepidine B & E and the four enzymes were obtained from the PubChem database and Protein databank. Results: Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of 0.59 ± 0.04, 0.57 ± 0.00 and 0.49 ± 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as a positive control. The major components of alkaloids of L. sativum, Lepidine B & E bind tightly to AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a noncompetitive inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent the HuAChE-induced Aβ aggregation. All the complexes of Lepidine B with the four enzymes show significant, several and different interactions. Conclusion: Our current study indicates that Lepidine B & E are promising anti-AD drugs and might become drug candidates to prevent Alzheimer's disease due to their multiple roles as potent inhibitors for AChE, BuChE, BACE, and MAGL. Indeed, they could inhibit Aβ fibrillogenesis. No previous results about the inhibitory effect of Lepidine B & E on the AChE, BuChE, β secretase, and monoacylglycerol lipase were reported.
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Molecular Docking, QSAR and Microscopic Studies of Anti-trypanosomal Compounds from the Pathogen Box
More LessBackground: Trypanosoma brucei (T. brucei) is the cause of the deadly human African trypanosomiasis (HAT) with a case fatality ratio of 10%. Objective: Targeting the essential Trypanosomal glucose metabolism pathway through the inhibition of phosphoglycerate kinase (PGK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a valid strategy for anti-T. brucei drug development. Methods: Here, quantitative structure activity relationship, molecular docking and microscopic studies were used to describe the mode of inhibition of selected compounds from the pathogen box PGK and GAPDH. Results: We identified 4 hit compounds from the pathogen box with optimal binding and chemical interactions. Notably, it was identified that interacting charge surface and atomic mass were key aspects of both PGK and GAPDH inhibition. Also, novel anti-trypanosomal compounds were identified from the pathogen box and their half maximal inhibitory concentrations were described. Conclusion: Our study presents new anti-trypanosomal compounds with optimal pharmacological profiles and an optimization strategy for improving target specificity in the rational design of novel anti-trypanosomal compounds.
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Structural Insights into the Molecular Design of ROS1 Inhibitor for the Treatment of Non-Small Cell Lung Cancer (NSCLC)
Authors: Ritu Adhikary, Ravina Khandelwal, Tajamul Hussain, Anuraj Nayarisseri and Sanjeev K. SinghBackground: Non-Small Cell Lung Cancer (NSCLC) alone is the leading cause of deaths worldwide. ROS1 is a receptor tyrosine kinase (RTK), eminently recognized as the stereotyped oncogenic driver. These RTKs trigger an array of physiological regulations via cellular signal transduction pathways, which are crucial for cancer development. This attributed ROS1 as an appealing and potential target towards the targeted cancer therapy. The present research aims to propound out an effective contemporary inhibitor for targeting ROS1 with a high affinity. Methods: Molegro Virtual Docker (MVD) provided a flexible docking platform to find out the bestestablished drug as an inhibitor for targeting ROS1. A similarity search was accomplished against the PubChem database to acquire the corresponding inhibitor compounds regarding the Entrectinib (Pub- Chem ID: 25141092). These compounds were docked to procure the high-affinity inhibitor for the target protein via virtual screening. A comparative study between the control molecule (PubChem ID: 25141092)and the virtual screened compound(PubChem ID-25175866) was performed for the relative analysis of their salient features, which involved pharmacophore mapping, ADMET profiling, and BOILED-Egg plot. Results: The virtual screened compound (PubChem ID-25175866) possesses the lowest rerank score (-126.623), and the comparative ADMET analysis also shows that it is a potential and effective inhibitor for ROS1 among the selected inhibitors. Conclusion: The present study provided a scope for the ROS1 inhibitor as significant prevention for nonsmall cell lung cancer (NSCLC). It can be upheld for future studies as a promising support via in vivo studies.
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Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophila: Identification, Characterization and Functional Exploration
Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn- MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, Xn- MazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.
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In Silico Design of Novel Sirtuin 1 Enzyme Activators for the Treatment of Age-related Diseases and Life Span
Authors: Tugba Ertan-Bolelli and Kayhan BolelliAim: The aim of the study was to develop new SIRT1 activator compounds, for this aim, we used virtual screening and molecular dynamics methods, which have been important tools for new hit compound searches. Background: Recently, with the progress of computing technology, it has been possible to obtain higher efficiency and lower costs for drug discovery. With in silico research and drug design, there is a reduction in time-consuming and expensive experimental work. An NAD+ dependent histone deacetylase enzyme, Sirtuin 1 (SIRT1), is involved in a variety of human disorders such as type II diabetes, cancer, obesity, and aging. Activation of SIRT1 could be useful for longevity and treating metabolic disorders. Objective: We used computational methods to develop new SIRT1 activator compounds. Methods: Firstly, virtual screening studies on the human SIRT1 enzyme were carried out. We used approximately 150.000 commercially available compounds from the Zinc database, which include FDA-approved drugs. According to virtual screening results, we selected seven potent activators. Then we compared these hit compounds with known activators by using docking methods. One of these hit compounds, acebutolol, is an FDA-approved drug, and was selected for additional studies using molecular dynamics simulations. Results: Seven hit compounds were identified with database screening. Each showed strong interactions with SIRT1, and acebutolol formed H-bonds with the important active site residues, Asn226 and/or Glu230 during the dynamics simulation. Conclusion: Based on our in silico studies, the seven most promising compounds, especially acebutolol, showed promising SIRT1 activator potency. The results may be used to design new selective and more potent SIRT1 activator drugs.
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Fragment-based Discovery of Potential Anticancer Lead: Computational and in vitro Studies
More LessBackground: The human epidermal growth factor receptor 2 (HER2) plays a role in the propagation of different types of cancers. It was identified in many types of cancer tissues like; breast, ovarian, lung, prostate, and stomach cancers. Therefore, inhibition of HER2 can lead to the discovery of novel anticancer agents. Objective: The study aims to discover a lead scaffold with drug-like properties and high affinity toward HER2. Methods: A list of HER2 inhibitors were collected, analyzed, and subjected to fragmentation and molecular docking. The in silico study computed the affinity, clash score, and ligand entropy score. A pharmacophore model for an ideal inhibitor designed, and tested against breast, lung, and prostatic cancer cell lines. Results: The discovered lead compound achieved several hydrogen bonds with the primary residues found in the active site of HER2, such as; Met801, Gln99, Lys753, and Thr862 with a computational affinity – 13.45 kcal/mol. In addition to a hydrophobic interaction with leu800. The in vitro cytotoxic activity against; breast cancer MCF-7, prostatic cancer PC-3 and lung cancer A-549 cell lines showed (IC50 = 86.38 ±1.1 mmol/ml), (IC50 = 157.02 ±1.3 mmol/ml), and (IC50 = 181.1 ±2.4 mmol/ml) respectively. Conclusion: The discovered lead is an excellent drug-like candidate for further development and optimization.
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Molecular Docking Studies of Glycyrrhetinic Acid Derivatives as Anti- Colorectal Cancer Agents
Authors: Nam Q.H. Doan, Tuyen N. Truong and Phuong T.V. NguyenBackground: In this study, the anti-colorectal cancer (CRC) activities of 40 glycyrrhetinic acid derivatives were proposed and evaluated by the molecular docking method, which allowed the flexibility of both ligand-receptor, with twelve CRC-related targets. Methods: The proposed derivatives, which clearly distinguish isomers at position 18 as well as the different tautomers, were divided into five groups, including (1) glycyrrhetinic acid and its oxidation derivatives, (2) glycoside derivatives, (3) 3β-amine derivatives, (4) five-membered heterocyclic ring-combined derivatives, and (5) six-membered heterocyclic ring-combined derivatives. Results: Finally, four out of twelve proposed targets related to CRC with good binding affinities to the proposed glycyrrhetinic acid derivatives were selected, including Epidermal Growth Factor Receptor (EGFR), Focal Adhesion Kinase (FAK), Lactate Dehydrogenase A (LDHA), and Thymidylate Synthase (TS). Conclusion: From there, 9/40 derivatives for EGFR (pKd ≥ 9); 10/40 derivatives for FAK (pKd ≥ 10); 9/40 derivatives for LDHA (pKd ≥ 10), and 6/40 derivatives for TS (pKd ≥ 9) were also obtained. The glycoside derivatives showed the best binding affinity (especially the glucuronide derivative 5b), followed by the 3β-amino derivatives (especially the 3β-(phenylamino) derivative 8b) and the five-membered heterocyclic ring-combined derivatives (especially the pyrrole derivative 10a or pyrazole derivative 11.2a), while the six-membered heterocyclic ring-combined derivatives had less potential to inhibit the 4 selected targets.
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Multi-objective Genetic Algorithm for De Novo Drug Design (MoGADdrug)
Authors: R. V. Devi, S. Siva Sathya and Mohane S. CoumarBackground: A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been proposed in this paper for the design of novel drug-like molecules similar to some reference molecules. The algorithm developed accepts a set of fragments extracted from approved drugs and available in fragment libraries and combines them according to specified rules to discover new drugs through the in-silico method. Methods: For this process, a genetic algorithm has been used, which encodes the fragments as genes of variable length chromosomes and applies various genetic operators throughout the generations. A weighted sum approach is used to simultaneously optimize the structural similarity of the new drug to a reference molecule as well as its drug-likeness property. Results: Five reference molecules namely Lidocaine, Furano-pyrimidine derivative, Imatinib, Atorvastatin and Glipizide have been chosen for the performance evaluation of the algorithm. Conclusion: Also, the newly designed molecules were analyzed using ZINC, PubChem databases and docking investigations.
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Development of a Lung Cancer Model in Wistar Rat and In Silico Screening of its Biomarkers
Authors: Nisat Alam, Hasina Najnin, Maidul Islam, Saleem Iqbal and Rana ZaidiBackground: Cancer is usually caused by three factors: Nutrition, inflammation and cigarette smoke. This study on rat experimental models would enable us to understand the mechanism of lung cancer caused by NNK to which humans are continuously exposed, help us understand possible molecular targets, and assist in designing drugs for humans against lung cancer. Aim: A lung cancer model was developed by administering tobacco-specific carcinogen: NNK [4- methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats for 24 weeks. Furthermore, in silico approach was followed to screen the molecular targets. Methods: A method was established in which subcutaneous and intraperitoneal injections of NNK were administered to male Wistar rats simultaneously. For authentication of lung cancer in vivo, we performed molecular docking simulations with protein biomarkers: Cox-2, p53, p38 MAPKs and EGFR using Hex-Discovery Studio, Schrödinger-maestro software. Results: Lung morphology and histopathology indicated the initiation of bronchiolar epithelial hyperplasia and squamous dysplasia in the cancer 1 group after 16 weeks of NNK exposure. 66.66% incidence of squamous cell carcinoma (SCC) and 33.3% incidence of adenocarcinoma were observed in cancer 2 group after being exposed to NNK. Results indicated that the incidence of SCC and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and from 33.33% to 42.58% in cancer 3 group, respectively. Docking results indicate the total binding energy and glide energy of Cox-2, p53, p38 MAPKs, EGFR : 38.14, -211.58, -181.58, -213.05 Kcal/mol and -39.25, -32.16,-36.49, -40.19 Kcal/mol, respectively. Conclusion: Pulmonary adenocarcinoma model was developed by administering tobacco-specific carcinogen: NNK [4-methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats in 24 weeks. In silico experiments confirmed EGFR to be the most potential target for NNK induced lung Cancer.
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Hispidin and Lepidine E: Two Natural Compounds and Folic Acid as Potential Inhibitors of 2019-novel Coronavirus Main Protease (2019- nCoVMpro), Molecular Docking and SAR Study
Authors: Talia Serseg, Khedidja Benarous and Mohamed YousfiBackground: 2019-nCoVis, a novel coronavirus was isolated and identified in 2019 in the city of Wuhan, China. On February 17, 2020 and according to the World Health Organization, 71, 429 confirmed cases worldwide were identified, among them 2162 new cases were recorded in the last 24 hours. One month later, the confirmed cases jumped to 179111, with 11525 new cases in the last 24 hours, with 7426 total deaths. No drug or vaccine is present at the moment for human and animal coronavirus. Methods: The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19. The 3CLpro (Mpro) is known for involving in counteracting the host innate immune response. Results: This work presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explains the main interactions in inhibitor-enzyme complex. Molecular docking study was carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E, and folic acid are bound tightly in the enzyme, therefore strong hydrogen bonds have been formed (1.69-1.80Å) with the active site residues. Conclusion: This study provides a possible therapeutic strategy for CoViD-19.
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Effect of the Intramolecular Hydrogen Bond on the Active Metabolite Analogs of Leflunomide for Blocking the Plasmodium falciparum Dihydroorotate Dehydrogenase Enzyme: QTAIM, NBO, and Docking Study
Authors: Reihaneh Heidarian and Mansoureh Zahedi-TabriziBackground: Leflunomide (LFM) and its active metabolite, teriflunomide (TFM), have drawn a lot of attention for their anticancer activities, treatment of rheumatoid arthritis and malaria due to their capability to inhibit dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. In this investigation, the strength of intramolecular hydrogen bond (IHB) in five analogs of TFM (ATFM) was analyzed employing density functional theory (DFT) using B3LYP/6-311++G (d, p) level and molecular orbital analysis in the gas phase and water solution. A detailed electronic structure study was performed using the quantum theory of atoms in molecules (QTAIM) and the hydrogen bond energies (EHB) of stable conformer obtained in the range of 76-97 kJ/mol, as a medium hydrogen bond. The effect of substitution on the IHB nature was studied by natural bond orbital analysis (NBO). 1H NMR calculations showed an upward trend in the proton chemical shift of the enolic proton in the chelated ring (14.5 to 15.7ppm) by increasing the IHB strength. All the calculations confirmed the strongest IHB in 5-F-ATFM and the weakest IHB in 2-FATFM. Molecular orbital analysis, including the HOMO-LUMO gap and chemical hardness, was performed to compare the reactivity of inhibitors. Finally, molecular docking analysis was carried out to identify the potency of inhibition of these compounds against PfDHODH enzyme. TFM acts as an inhibitor of dihydroorotate dehydrogenase (DHODH) and Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme. Leflunomide and its active metabolite teriflunomide have been identified as drugs for treatment of some diseases, such as multiple sclerosis (MS), rheumatoid arthritis (RA), malaria, and cancer. Hydrogen bonds play a key role in the interaction between drugs and enzymes. Objectives: The aim of the present work is to investigate the effect of the strength of intramolecular hydrogen bonds (IHBs) in the active metabolite analogs of leflunomide or analogs of teriflunomide (ATFMs) and study the interaction of these inhibitors against the PfDHODH enzyme using quantum mechanical methods. Methods: At first, intramolecular hydrogen bonds in five ATFMs were evaluated by the DFT method, quantum theory of atoms in molecules (QTAIM), nuclear magnetic resonance (NMR), natural bond orbital (NBO), and molecular orbital (MO) analyses. Then, the interaction of these inhibitors against the PfDHODH enzyme were compared using molecular docking study. Results: All the computed results confirm the following trend in the intramolecular hydrogen bond strength in five mono-halo-substituted 2-cyano-3-hydroxy-N-phenylbut-2-enamide (ATFM): 5-FATFM> 4-Br-ATFM ≈ 3-Br-ATFM>3-Cl-ATFM>TFM-Z>2-F-ATFM which is in agreement with QTAIM, NMR, and NBO results. Docking results show that 5-F-ATFM (EHB=97kJ/mol) has the minimum MolDock score due to its considerable IHB strength. Conclusion: For strong IHBs (EHB>100kJ/mol), C=O and O–H group are involved in the intramolecular interactions and do not contribute to the external interactions. Also, the docking study revealed maximum binding energy between TFM-Z and PfDHODH enzyme.
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Volumes & issues
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Volume 21 (2025)
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Volume 20 (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)
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