Turkish Computational and Theoretical Chemistry最新文献

{"title":"In-silico molecular docking, ADME study, and molecular dynamic simulation of new azetidin-2-one derivatives with antiproliferative activity","authors":"Aya Ahmed, Monther Faisal","doi":"10.33435/tcandtc.1498365","DOIUrl":"https://doi.org/10.33435/tcandtc.1498365","url":null,"abstract":"Over the past two decades, protein kinase has been a heavily studied target in the development of new anti-proliferative medications. Heterocyclic systems have been identified as the preferred scaffold because of their wide range of biological properties. In this research, the objective was to design and develop fifteen novel azetidin-2-one derivatives and assess their cytotoxic potential as inhibitors of the epidermal growth factor receptor, which is considered one of the key factors influencing cell growth and proliferation. The crystal structure of inactive EGFR tyrosine kinase domain ligand erlotinib from protein data bank was retrieved in order to be docked with our proposed azetidine-2-one derivatives to evaluate their activity as anti-proliferative agents. In this article, an in-silico molecular docking approach proposes that these azetidine-2-one derivatives have satisfactory binding contact with the erlotinib binding site. Although, three compounds have been identified as the most powerful as they have PLP fitness scores of (77.79, 76.68 and 71.46), respectively, while the reference ligand’s fitness score was (71.94). Additionally, all of our derivatives have satisfied the Swiss-ADME parameters, indicating that they may be orally active compounds. In conclusion, two compounds (A-2 and A-8) have better PLP fitness, and one (A-14) has a comparable score in comparison to the reference ligand, at the active site of epidermal growth factor receptor. indicating that the novel azetidine-2-one derivatives have shown interesting results and could be used as model compounds to create novel anti-proliferative drugs. However, more pharmacological evaluation is needed.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141813580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Evaluation of Molecular Docking, Molecular Dynamic, and ADME Study of New Nabumetone Schiff Base Derivatives (1,3,4-oxadiazole or 1,3,4-thiadiazole ring) Promising Antiproliferation Action Against Lung Cancer","authors":"Ahmed Haloob, Monther Faisal, Ayad Mr Raauf","doi":"10.33435/tcandtc.1494129","DOIUrl":"https://doi.org/10.33435/tcandtc.1494129","url":null,"abstract":"A total of eight novel Nabumetone Schiff Base Derivatives with 1,3,4-oxadiazole or 1,3,4-thiadiazole rings have been proposed to evaluate their potential effectiveness against the epidermal growth factor receptor (EGFR). Molecular docking was conducted with the crystalline structure of EGFR (code: 4HJO), wherein the eight compounds of Nabumetone Schiff Base Derivatives with 1,3,4-oxadiazole or 1,3,4-thiadiazole ring derivatives docked to determine their binding affinity to the target binding site. Using GOLD software (CCDC) version 5.43, computer predictions were made, and the compounds were designed using ChemDraw version 22.2 (professional version). Subsequently, their selectivity with EGFR was assessed, with erlotinib selected as a control for comparison. In silico ADME studies were conducted, revealing the significant potential for binding, and drug-likeness was assessed using the Swiss ADME website. Additionally, Molecular Dynamic simulations of compound N3 complexes with EGFR were performed using Schrodinger Suite 2023 software for 50 ns, estimating RMSD, RMSF, Ligand-Protein Contacts, and Ligand Torsion Profile results. Result Showing the best binding energy within receptor pocket with a promising activity against EGFR protein receptor. The highest PLP fitness levels were found in compounds N1, N2, and N3 for lung cancer cell protein (89.1, 89.02, and 87.95, respectively, average value), All compounds were found to adhere to Lipinski's rule of five, with high absorption from the gastrointestinal tract (except N4), and none of the proposed compounds were able to pass through the blood-brain barrier. Molecular dynamic result, Mean Protein RMSD 1.8 Å, ligand RMSD 1.6 Å, and RMSF reveals that the protein amino acids interacting with the ligand remain within a distance of less than 1 Å. In conclusion, these findings offer a promising direction for the development of effective treatments for lung cancer","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Computational Approach of Anti-diabetic Potential Evaluation of Flower and Seed of Nyctanthes arbor tristis Linn","authors":"R. Shrestha, N. Parajuli, P. Neupane, S. Dhital, B. Maharjan, T. Shrestha, S. Bharati, B. Marasini, J. Adhikari Subin","doi":"10.33435/tcandtc.1487560","DOIUrl":"https://doi.org/10.33435/tcandtc.1487560","url":null,"abstract":"Exploring the medicinal significance of bioactive compounds through computational methods is an increasingly practiced approach in contemporary medicinal research. This study aims to assess the antidiabetic potential of compounds extracted from the plant Nyctanthes arbor tristis by evaluating their ability to inhibit the carbohydrate metabolic enzyme α-glucosidase. The research work was conducted through molecular docking calculation, molecular dynamics simulation (MDS), and ADMET prediction techniques. Among the compounds, arbortistoside-C (NAS03), and arbortristoside-D (NAS04) found in the seed of the plant were identified as hit inhibitors of the target protein with docking scores, -9.9 and -9.4 kcal/mol, respectively. The compounds showed a comparable docking score with the drug of diabetes acarbose (-8.6 kcal/mol). Geometrical parameters like radius of gyration, solvent accessibility surface, root mean square deviation, and root mean square fluctuation from MDS supported the stability of the protein-ligand complex. MMPBSA calculations demonstrated the stability and feasibility of the complex with binding free energy changes of -29.06±6.06 and -23.58±8.80 kcal/mol for compounds NAS03 and NAS04, respectively. The ADMET prediction suggested the drug-likeness of the compounds compared with that of the standard drugs. The results could be used in proposing the antidiabetic potential of the two compounds from the plant as a potential inhibitors of α-glucosidase enzyme. Further, in vitro and in vivo experiments on such compounds could be a more reliable path to validate the output of this computational research.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The discovery of new potent VEGFR2 inhibitors for potential anti-angiogenesis agent through a combination of structure-based virtual screening, molecular dynamics simulation and ADME-Tox prediction","authors":"H. Boucherit, Amina Merzoug, Ilham Boulhissa, Asma Mosbah, Abderrahmane Bensegueni","doi":"10.33435/tcandtc.1437517","DOIUrl":"https://doi.org/10.33435/tcandtc.1437517","url":null,"abstract":"The discovery of the importance of angiogenesis in the mechanisms of tumor growth has empowered the improvement of new particles that are utilized in the therapy of various cancers. The goal of this research was to identify novel compounds functioning as potent VEGFR2 inhibitors in silico. It is an interesting therapeutic target for developing new anti-angiogenic drugs. In this work, molecular simulation studies of enzyme inhibition was carried out by structure-based virtual screening with FlexX program of VEGFR2. This approach makes it possible to model the interactions between a protein and thousands of small chemical compounds. A collection of 6,000 compounds originating from the ZINC chemical library, were tested against the active site of VEGFR2. The ADME-Tox characteristics and molecular dynamics simulation of the potential compounds were also examined. At the end of this screening, the compounds ZINC01534124 and ZINC00588595 appear as new inhibitors theoretically more active towards VEGFR2. Again, these inhibitors have shown significant binding energy by interacting with important residues in the active site. Furthermore, the in silico prediction of a similar drug positively informs us about the ADME-Tox properties of these new compounds. Finally, the stable binding of VEGFR2 with ZINC01534124 and ZINC00588595 is shown using 100 ns molecular dynamics simulations. These findings point to the chemicals ZINC01534124 and ZINC00588595 as potential candidates for VEGFR2 inhibitor research. They might also act as a starting point for further chemical modifications in order to produce therapeutically relevant anti-angiogenic medications.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141375510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Potential Pharmacological Applications of 5-Hydroxy-2 (hydroxymethyl)-4H pyran-4 one through Electronic Characterization and MM-GBSA Studies for Oxidative Stress and Tyrosinase Inhibition: A Quantum Chemical Approach","authors":"Attar Kubaib, N. N. Afroze, Mohamed Imran Predhanekar","doi":"10.33435/tcandtc.1381982","DOIUrl":"https://doi.org/10.33435/tcandtc.1381982","url":null,"abstract":"The study thoroughly examines the possible applications of 5 Hydroxy – 2 (hydroxymethyl) – 4 H pyran – 4 one. Through Quantum chemical analysis, the research rigorously evaluates the compound's properties, including its optoelectronics, geometrical structure, and intermolecular interactions. The geometrical structure parameters were optimized using a 6–311++G(d,p) basis set in the DFT/B3LYP method, and the resulting geometrical factors were then scaled to calculate probable vibrational wavenumbers. The Mulliken charges and MEP map were used to locate electrophilic, nucleophilic regions, and chemical reactivity was described using FMOs and Fukui function assessments. The multiwfn was employed to investigate topological analysis (surface distance projection and Hirshfeld maps). The UV-visible spectrum was used to estimate the absorption of maximum wavelengths, which was then correlated with the TD-DFT, DOS, and band structure investigations. The study also calculated parameters, including Total Energies, ZPE, Entropy, Dipole moment, and Heat Capacity for monomeric and dimeric units. Pharmacokinetics were used to determine the biological characteristics of the compound. The MM-GBSA simulation was performed, and the results suggest that this compound has the potential to be an enhancing anti-oxidant protection agent due to its high binding affinity and intermolecular interactions. These findings are crucial in developing therapeutic agents with pharmacological effects and potential toxicities.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141117775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A DFT-D investigation of the energetic and structural aspects of dehydrogenation of methanol on a bimetallic surface PtGe(110) exploring the germanium effect on the anti-poisoning of pt(110) catalytic activity","authors":"Abdellatif Hassak, R. Ghailane","doi":"10.33435/tcandtc.1399682","DOIUrl":"https://doi.org/10.33435/tcandtc.1399682","url":null,"abstract":"Platinum is the most active pure metal for dehydrogenating methanol to create hydrogen, which is crucial for fuel cells. However, one significant disadvantage that reduces the effectiveness and long-term performance of platinum catalysts is their susceptibility to CO poisoning. In the current study, we examine and elucidate the promotional impact of Ge on Pt catalysts with increased resistance to deactivation by CO poisoning. We do this by combining partial density of states calculations with electronic configuration and Mulliken atomic charges. The self-consistent periodic density functional theory with dispersion correction (DFT-D) was used to investigate the methanol adsorption and dehydrogenation mechanisms on the surface of PtGe (110). On the surface, several adsorption mechanisms of pertinent intermediates were found. Furthermore, a thorough analysis of a reaction network comprising four reaction paths revealed that, in terms of activation barriers, the first O—H bond scission of CH3OH appears to be more advantageous than C—H bond cleavage on the PtGe(110) surface. Additionally, it has been demonstrated that the main route on the PtGe(110) surface is CH3OH→CH3O→CH2O→CHO→CO evolution. The remarkable differences in the predominant reaction pathway on the Pt(110) surface, and PtGe(110) surface indicate that the Ge-doped Pt Nano catalyst is more selective and resistant to deactivation.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141116561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Anticancer Properties of 2-benzylidene-1-indanone and Its Derivatives by DFT and Molecular Docking","authors":"Ceylan Alkaya Yıldız, S. Erkan","doi":"10.33435/tcandtc.1399916","DOIUrl":"https://doi.org/10.33435/tcandtc.1399916","url":null,"abstract":"In this study, 2-benzylidene-1-indanone and its derivatives, which is a chalcone compound and contains indanone in its structure, were examined. Quantum chemical parameters for these compounds were calculated with the B3LYP method and the 6-31G(d) basis set and evaluated for their biological activity. The effect of different functional groups (F, Cl, Br, CF3, CH3 and OCH3) attached to the 2-benzylidene-1-indanone compound on biological activity was investigated. Some quantum chemical parameters such as highest energy filled molecule orbital energy (EHOMO), lowest non-bonding empty molecule orbital energy (ELUMO), energy gap (ΔE), hardness (η), softness (σ), global molecular electrophilicity (ω) index, global molecular nucleophilicity (ɛ) index, electron-accepting (ω+) and electron-donating (ω-) electrophilicity index were calculated for the biological activities of the compounds. Frontier molecular orbitals and molecular electrostatic potential (MEP) maps were interpreted. The biological activities of 2-benzylidine-1-indanone and some of its derivatives bearing the 1-indanone skeleton were evaluated by performing molecular docking studies with the target protein PDB ID = 1HJD corresponding to the melanoma cell line. The activity ranking obtained with quantum chemical parameters was found to be compatible with the binding energies obtained from docking results.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141115441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could Zingiber officinale plant be effective against Omicron BA.2.75 of SARS-CoV-2?","authors":"H. Saraç, Ahmet Demi̇rbaş, Burak Tüzün","doi":"10.33435/tcandtc.1198612","DOIUrl":"https://doi.org/10.33435/tcandtc.1198612","url":null,"abstract":"Zingiber officinale plant was examined in this study. The chemicals found in this plant were identified using the GC-MS method. The activities of the determined chemical molecules against the SARS-CoV-2 Omicron variant were compared. We focused to determine whether Zingiber officinale plant would be an inhibitor against Omicron of SARS-CoV-2 in silico. As a result of theoretical calculations, Zingiber officinale plant was found to contain many chemicals as a result of GC-MS analysis. These chemicals were detected one by one and their activity values were calculated for the SARS-CoV-2 virus. As a result, molecules with high activity were detected. ADME/T properties were investigated in order to examine the drug properties of molecules with high activity. According to ADME/T results, these five molecules examined are suitable for use in human metabolism as drug molecules.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73910294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DFT , Monte Carlo and Molecular Dynamics modeling of the Carvacrol, Camphor and Linalool /Al(111) Interaction","authors":"Fathia Lai̇hemdi̇, A. Barhoumi̇, Brahim Li̇zoul, Kamilia Mouni̇ch, Tariq Benabbouha, Mohammed Chafi, A. Zeroual, El İdrissi Mohammed","doi":"10.33435/tcandtc.1286725","DOIUrl":"https://doi.org/10.33435/tcandtc.1286725","url":null,"abstract":"In this work, the interaction of three natural compounds: carvacrol (Inh-1), camphor (Inh-2), and linalool (Inh-3) on the Al(111) surface have been studied using DFT/B3LYP/6-31G(d,p), to understand adsorption behavior on the metal surface. The results obtained show a strong correlation between the inhibitory efficiency (IE%) of aluminum corrosion and the quantum chemical parameters of reactivity derived from DFT. In addition, the interactions between the three natural inhibitors and the aluminum surface were studied using Monte Carlo (MC) and molecular dynamics simulations, as a result, the three molecules have strong interactions with the metal surface and thus have excellent predictive power for inhibition against metal corrosion, the three corrosion inhibitors have higher inhibitory efficiency and can be used as inhibitors to minimize the corrosion rate of the metal, therefore, the efficiency of Inh-1 is more important than the efficiency of Inh-2 and Inh-3.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139278244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Binding Profiles of Curcumin Derivatives to G-Quadruplex (G4) Structures Found in Human Oncogene Promoters","authors":"H. S. Portakal","doi":"10.33435/tcandtc.1318067","DOIUrl":"https://doi.org/10.33435/tcandtc.1318067","url":null,"abstract":"G-Quadruplex (G4) structures are special significant DNA topologies formed by accumulation of G-tetrads which are planar structures of four guanine residues interacting with hydrogen bonds through Hoogsten edges around monovalent cations such as potassium (K) or sodium (Na). While these special topologies are mostly observed in telomere regions, they might be found over regulatory regions of the genes such as promoter, enhancer etc. In addition, since that various oncogenes carry G4 structures over their promoters, it’s highlighted that G4s have significant role over cancer prognosis through regulation of expression level. To date, binding profiles of curcumin having great antioxidant and anti-inflammatory properties and its derivatives to G4s found in telomere regions and promoter of c-Myc were discovered. As such, to discover selective binding profiles of curcumin derivatives to G4s found in promoters of various oncogenes such as c-Myc, c-KIT, hTERT, RET, VEGF, and PARP1 have quite potential in the drug design for several cancer types. In light of these information, 18 curcumin derivatives from ZINC15 database were docked to related G4 structures. ADME and toxicity properties of all derivatives were analyzed and biological reactivity as well as molecular electrostatic surface potential (MESP) features of totally 4 derivatives (C11, C13, C14, and C15) exhibiting selective binding pattern to certain G4s were analyzed with density functional theory (DFT) method.","PeriodicalId":36025,"journal":{"name":"Turkish Computational and Theoretical Chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139281232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}