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The evolutionarily conserved extracellular signal-regulated kinase 2 (ERK2) is involved in regulating cellular signaling in both normal and pathological conditions. ERK2 expression is critical for human development, while hyperactivation is a major factor in tumor progression. Up to now, there have been no approved inhibitors that target ERK2, and as such, here we report on screening of a naturally occurring plant-based anticancerous compound-activity-target (NPACT) database for prospective ERK2 inhibitors. More than 1,500 phytochemicals were screened using in-silico molecular docking and molecular dynamics (MD) approaches. NPACT compounds with a docking score lower than a co-crystallized LHZ inhibitor (calc.-10.5 kcal/mol) were subjected to MD simulations. Binding energies (ΔGbinding) of inhibitor-ERK2 complexes over the MD course were estimated using an MM-GBSA approach. Based on MM-GBSA//100 ns MD simulations, the steroid zhankuic acid C (NPACT01034) demonstrated greater binding affinity against ERK2 protein than LHZ, with ΔGbinding values of -50.0 and -47.7 kcal/mol, respectively. Structural and energetical analyses throughout the MD course demonstrated stabilization of zhankuic acid C complexed with ERK2 protein. The anticipated ADMET properties of zhankuic acid C indicated minimal toxicity. Moreover, in-silico evaluation of fourteen ERK2 inhibitors in clinical trials demonstrated the higher binding affinity of zhankuic acid C towards ERK2 protein.
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Nanotechnology is an emerging technology that uses medicinal plants to extract nanoparticles for conventional applications. In the present investigation, the medical plant Tulsi (Ocimum sanctum) has used in the synthesis of cobalt (Co) nanoparticles in a cost-effective, feasible process. The efficiency of nanoparticles in removing methyl orange dye was evaluated by analyzing their applications in wastewater treatment. An analysis of the anti-inflammatory and anti-cancer properties of Tulsi-mediated Co nanoparticles was conducted to examine their medical application. Morphological analysis of Co nanoparticles showed that the synthesized nanoparticles were in crystal shape with a mean particle size of 110 nm. A batch adsorption study has shown that incubation periods of 5 h, pH 2, temperatures of 70 °C, and adsorbent dosage of 125 µg/mL are optimal for removing methyl orange dye from wastewater. To examine the anti-inflammatory properties of Tulsi-mediated Co nanoparticles, protein denaturation and nitric oxide scavenging assays were performed. The maximum anti-inflammatory response was recorded at a concentration of 250 µg/mL of Co nanoparticles. MTT assays against MDA-MB-231 human breast cancer cells were used to evaluate the anti-cancer properties of Co nanoparticles. This study investigates the economical extraction of Co nanoparticles from tulsi and its potential use in wastewater purification and biomedical applications.
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In recent decades, Technology and Innovation (TI) have shown tremendous potential for improving agricultural productivity and environmental sustainability. However, the adoption and implementation of TI in the agricultural sector and its impact on the environment remain limited. To gain deeper insights into the significance of TI in enhancing agricultural productivity while maintaining environmental balance, this study investigates 21 agriculture-dependent Asian countries. Two machine learning techniques, LASSO (Least Absolute Shrinkage and Selection Operator) and Elastic-Net, are employed to analyze the data, which is categorized into three regional groups: ASEAN (Association of Southeast Asian Nations), SAARC (South Asian Association for Regional Cooperation), and GCC (Gulf Cooperation Council). The findings of this study highlight the heterogeneous nature of technology adoption and its environmental implications across the three country groups. ASEAN countries emerge as proactive adopters of relevant technologies, effectively enhancing agricultural production while simultaneously upholding environmental quality. Conversely, SAARC countries exhibit weaker technology adoption, leading to significant fluctuations in environmental quality, which in turn impact agricultural productivity. Notably, agricultural emissions of N2O (nitrous oxide) and CO2 (carbon dioxide) in SAARC countries show a positive association with agricultural production, while CH4 (methane) emissions have an adverse effect. In contrast, the study reveals a lack of evidence regarding technological adoption in agriculture among GCC countries. Surprisingly, higher agricultural productivity in these countries is correlated with increased N2O emissions. Moreover, the results indicate that deforestation and expansion of cropland contribute to increased agricultural production; however, this expansion is accompanied by higher emissions related to agricultural activities. This research represents a pioneering empirical analysis of the impact of TI and environmental emission gases on agricultural productivity in the three aforementioned country groups. It underscores the imperative of embracing relevant technologies to enhance agricultural output while concurrently ensuring environmental sustainability. The findings of this study provide valuable insights for policymakers and stakeholders in formulating strategies to promote sustainable agriculture and technological advancement in the context of diverse regional dynamics.
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Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Solo , Agricultura/métodos , Gases , Dióxido de Carbono/análise , Tecnologia , Metano/análise , Óxido Nitroso/análiseRESUMO
The potentiality of the ß12 borophene (ß12) and pristine graphene (GN) nanosheets to adsorb tetrahalomethanes (CX4; X = F, Cl, and Br) were investigated using density functional theory (DFT) methods. To provide a thorough understanding of the adsorption process, tetrel (XC-X3âââß12/GN)- and halogen (X3C-Xâââß12/GN)-oriented configurations were characterized at various adsorption sites. According to the energetic manifestations, the adsorption process of the CX4âââß12/GN complexes within the tetrel-oriented configuration led to more desirable negative adsorption energy (Eads) values than that within the halogen-oriented analogs. Numerically, Eads values of the CBr4âââBr1@ß12 and T@GN complexes within tetrel-/halogen-oriented configurations were -12.33/-8.91 and -10.03/-6.00 kcal/mol, respectively. Frontier molecular orbital (FMO) results exhibited changes in the EHOMO, ELUMO, and Egap values of the pure ß12 and GN nanosheets following the adsorption of CX4 molecules. Bader charge transfer findings outlined the electron-donating property for the CX4 molecules after adsorbing on the ß12 and GN nanosheets within the two modeled configurations, except the adsorbed CBr4 molecule on the GN sheet within the tetrel-oriented configuration. Following the adsorption process, new bands and peaks were observed in the band structure and density of state (DOS) plots, respectively, with a larger number in the case of the tetrel-oriented configuration than in the halogen-oriented one. According to the solvent effect affirmations, adsorption energies of the CX4âââß12/GN complexes increased in the presence of a water medium. The results of this study will serve as a focal point for experimentalists to better comprehend the adsorption behavior of ß12 and GN nanosheets toward small toxic molecules.
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BRD4 (bromodomain-containing protein 4) is an epigenetic reader that realizes histone proteins and promotes the transcription of genes linked to cancer progression and non-cancer diseases such as acute heart failure and severe inflammation. The highly conserved N-terminal bromodomain (BD1) recognizes acylated lysine residues to organize the expression of genes. As such, BD1 is essential for disrupting BRD4 interactions and is a promising target for cancer treatment. To identify new BD1 inhibitors, a SuperDRUG2 database that contains more than 4600 pharmaceutical compounds was screened using in silico techniques. The efficiency of the AutoDock Vina1.1.2 software to anticipate inhibitor-BRD4-BD1 binding poses was first evaluated based on the co-crystallized R6S ligand in complex with BRD4-BD1. From database screening, the most promising BRD4-BD1 inhibitors were subsequently submitted to molecular dynamics (MD) simulations integrated with an MM-GBSA approach. MM-GBSA computations indicated promising BD1 binding with a benzonaphthyridine derivative, pyronaridine (SD003509), with an energy prediction (ΔGbinding) of -42.7 kcal/mol in comparison with -41.5 kcal/mol for a positive control inhibitor (R6S). Pharmacokinetic properties predicted oral bioavailability for both ligands, while post-dynamic analyses of the BRD4-BD1 binding pocket demonstrated greater stability for pyronaridine. These results confirm that in silico studies can provide insight into novel protein-ligand regulators, specifically that pyronaridine is a potential cancer drug candidate.
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Simulação de Dinâmica Molecular , Proteínas Nucleares , Simulação de Acoplamento Molecular , Proteínas Nucleares/metabolismo , Proteínas que Contêm Bromodomínio , Fatores de Transcrição/metabolismo , Ligantes , Proteínas de Ciclo Celular/metabolismoRESUMO
Novel one-pot multicomponent synthesis of 2-pyrimidinamine derivatives can be achieved via green chemistry, using Cu(II)-tyrosinase enzyme (Cu-Tyr) as a catalyst. This method offers mild reaction conditions and a high yield of derivatives. We synthesised several compounds in this manner and evaluated their larvicidal, and antifeedant activities. Out of the synthesised derivatives, compound 3, with a median lethal dose (LD50) of 21.43 µg/mL, was highly active against Culex quinquefasciatus, compared to compounds 1a-m and 2, and the control, hydantocidin. Compounds 1j, 1d, and 1e were low active against C. quinquefasciatus with LD50 values of 78.46, 78.59, and 79.54 µg/mL, respectively. In antifeedant screening, compounds 1j, 1l, and 2 generated 100% mortality within 24 h against Oreochromis mossambicus at 100 µg/mL, where toxicity was determined as the ratio of the number of dead and live fingerlings (%) at 24 h. In contrast, compounds 1a-f, 1i, 1m, and 3 were less toxic to O. mossambicus as compared to the control, dibromoisophakellin. Therefore, compound 3 had high larvicidal activity against C. quinquefasciatus and was less toxic to non-target aquatic species. Molecular docking studies also supported the finding that compound 3 was an effective larvicide with more inhibition ability than the control hydantocidin (-9.6 vs. -6.1 kcal/mol).
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Cobre/química , Culex/efeitos dos fármacos , Química Verde/métodos , Inseticidas/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Animais , Comportamento Alimentar , Larva/efeitos dos fármacos , Pirimidinas/química , Tilápia , Testes de ToxicidadeRESUMO
Lead (Pb) is thought to be one of most injurious metals on the earth. Lead stress in plants enhances synthesis of highly toxic reactive oxygen species (ROS). During present research, impact of calcium-oxide nanoparticles (CaO-NPs) was observed on antioxidative defense mechanism in Abelmoschus esculentus plants prone to Pb stress. A CRD experiment was employed with 5 replicates having four treatments (T0 = Control, T1 = Pb stress (200 ppm), T2 = CaO-NPs and T3 = Pb + CaO-NPs). Pb-stressed seedlings exhibited decreased root growth, shoot growth, chlorophyll concentration and biomass accumulation. Moreover, higher synthesis of hydrogen-peroxide (H2O2), malondialdehyde (MDA) and electrolyte leakage (EL) resulting in cellular injuries were noted in plants growing in Pb spiked conditions. Similarly, stressed plants showed higher accumulation of total soluble sugar and proline content besides elevated activity of antioxidative enzymes counting catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and ascorbate peroxidase (APX). On the contrary side, CaO-NPs alleviated the Pb induced phytotoxicity through improving activity of antioxidative enzymes. The elevated activity of antioxidant enzymes reduced biosynthesis of H2O2 and MDA which was revealed through the increased growth parameters. In addition, CaO-NPs persuaded enhancement in plant defence machinery by decreased chlorophyll deprivation and augmented the uptake of plant nutrients including K and Ca content. Hence, CaO-NPs can be potent regulators of the antioxidative enzymes and stress markers to ameliorate abiotic stresses.
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Abelmoschus , Compostos de Cálcio , Nanopartículas , Óxidos , Antioxidantes/metabolismo , Abelmoschus/metabolismo , Peróxido de Hidrogênio , Chumbo , Estresse Oxidativo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Clorofila , Plântula/metabolismoRESUMO
Herein, the potential of ZO3 and ZF2 aerogen-comprising molecules (where Z = Ar, Kr, and Xe) to engage in σ-, lp-, and π-hole site-based interactions was comparatively studied using various ab initio computations. For the first time, a premier in-depth elucidation of the external electric field (EEF) influence on the strength of the σ-, lp-, and π-hole site-based interactions within the ZO3/ZF2â¯NH3 and â¯NCH complexes was addressed using oriented EEF with disparate magnitude. Upon the energetic features, σ-hole site-based interactions were noticed with the most prominent preferability in comparison to lp- and π-hole analogs. This finding was ensured by the negative interaction energy values of -11.65, -3.50, and -2.74 kcal mol-1 in the case of σ-, lp-, and π-hole site-based interactions within the XeO3⯠and XeF2â¯NH3 complexes, respectively. Detailedly, the strength of the σ- and lp-hole site-based interactions directly correlated with the atomic size of the aerogen atoms and the magnitude of the positively oriented EEF. Unexpectedly, an irregular correlation was noticed for the interaction energies of the π-hole site-based interactions with the size of the π-hole. Interestingly, the π-hole site-based interactions within Kr-comprising complexes exhibited higher negative interaction energies than the Ar- and Xe-comprising counterparts. Notwithstanding, a direct proportion between the interaction energies of the π-hole site-based interactions and π-hole size was obtained by employing EEF along the positive orientation with high strength. The present outcomes would be a fundamental basis for forthcoming progress in studying the σ-, lp-, and π-hole site-based interactions within aerogen-comprising complexes and their pertinent applications in materials science and crystal engineering.
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The efficacy of aluminium phosphide (Al12P12) nanocage toward sensing methanol (MeOH) and ethanol (EtOH) volatile organic compounds (VOCs) was herein thoroughly elucidated utilizing various density functional theory (DFT) computations. In this perspective, MeOH⯠and EtOHâ¯Al12P12 complexes were investigated within all plausible configurations. According to the energetic features, the EtOHâ¯Al12P12 complexes exhibited larger negative values of adsorption and interaction energies with values up to -27.23 and -32.84 kcal mol-1, respectively, in comparison to the MeOHâ¯Al12P12 complexes. Based on the symmetry-adapted perturbation theory (SAPT) results, the electrostatic forces were pinpointed as the predominant component beyond the adsorption process within the preferable MeOH⯠and EtOHâ¯Al12P12 complexes. The findings of the noncovalent interaction (NCI) index and quantum theory of atoms in molecules (QTAIM) outlined the closed-shell nature of the interactions within the studied complexes. Substantial variations were found in the molecular orbitals distribution patterns of MeOH/EtOH molecules and Al12P12 nanocage, outlining the occurrence of the adsorption process within the complexes under investigation. Thermodynamic parameters were denoted with negative values, demonstrating the spontaneous exothermic nature of the most favorable complexes. New energy states were observed within the extracted density of states plots, confirming the impact of adsorbing MeOH and EtOH molecules on the electronic properties of the Al12P12 nanocage. The appearance of additional peaks in Infrared Radiation (IR) and Raman spectra revealed the apparent effect of the adsorption process on the features of the utilized sensor. The emerging results declared the potential uses of Al12P12 nanocage as a promising candidate for sensing VOCs, particularly MeOH and EtOH.
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Liver diseases pose a significant global health burden, with limited therapeutic options for chronic cases. Zinc oxide (ZnO) nanomaterials have emerged as promising candidates for hepatoprotection due to their antioxidant, anti-inflammatory, and regenerative properties. However, their potential remains hampered by insufficient drug loading and controlled release. The current study explores the intercalation of Naproxen (Nx), a potent anti-inflammatory and analgesic drug, within ZnO stacked nanosheets (SNSs) to address these limitations. Herein, an easy and solution-based synthesis of novel Nx intercalated ZnO SNSs was established. The obtained Nx intercalated ZnO SNSs were encapsulated with poly(vinyl acetate) (PVA) to make them biocompatible. The synthesized biocomposite was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR), which confirm the successful synthesis and intercalation of Nx within the ZnO SNSs. The obtained outcomes showed that the configuration of ZnO nanosheets was altered when Nx was introduced, resulting in a more organized stacking pattern. An in vivo investigation of mice liver cells unveiled that the Nx intercalated ZnO SNss had increased hepatoprotective properties. The study's results provide valuable insights into using Nx intercalated ZnO SNss for targeted drug delivery and improved treatment effectiveness, particularly for liver-related illnesses.
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Herein, attempts were made to explore the adsorption prospective of beryllium oxide (Be12O12) and boron nitride (B12N12) nanocarriers toward the temozolomide (TMZ) anticancer drug. A systematic investigation of the TMZ adsorption over nanocarriers was performed by using quantum chemical density functional theory (DFT). The favorability of Be12O12 and B12N12 nanocarriers toward loading TMZ was investigated through AâD configurations. Substantial energetic features of the proposed configurations were confirmed by negative adsorption (E ads) energy values of up to -30.47 and -26.94 kcal/mol for TMZâ¢â¢â¢Be12O12 and â¢â¢â¢B12N12 complexes within configuration A, respectively. As per SAPT results, the dominant contribution beyond the studied adsorptions was found for the electrostatic forces (E elst = -100.21 and -63.60 kcal/mol for TMZâ¢â¢â¢B12N12 and â¢â¢â¢Be12O12 complexes within configuration A, respectively). As a result of TMZ adsorption, changes in the energy of molecular orbitals followed by alterations in global reactivity descriptors were observed. Various intermolecular interactions within the studied complexes were assessed by QTAIM analysis. Notably, a favorable adsorption process was also observed under the effect of water with adsorption energy ( reaching -28.05 and -22.26 kcal/mol for TMZâ¢â¢â¢B12N12 and â¢â¢â¢Be12O12 complexes within configuration A, respectively. The drug adsorption efficiency of the studied nanocarriers was further examined by analyzing the IR and Raman spectra. From a sustained drug delivery point of view, the release pattern of TMZ from the nanocarrier surface was investigated by recovery time calculations. Additionally, the significant role of doping by heavy atoms (i.e., MgBe11O12 and AlB11N12) on the favorability of TMZ adsorption was investigated and compared to pure analogs (i.e., Be12O12 and B12N12). The obtained data from thermodynamic calculations highlighted that the adsorption process over pure and doped nanocarriers was spontaneous and exothermic. The emerging findings provide a theoretical base for future works related to nanocarrier applications in the drug delivery process, especially for the TMZ anticancer drug.
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σ-Hole site-based interactions in the trigonal bipyramidal geometrical structure of hypervalent pnicogen, halogen, and aerogen-bearing molecules with pyridine and NCH Lewis bases (LBs) were comparatively examined. In this respect, the ZF5···, XF3O2···, and AeF2O3···LB complexes (where Z = As, Sb; X = Br, I; Ae = Kr, Xe; and LB = pyridine and NCH) were investigated. The electrostatic potential (EP) analysis affirmations outlined the occurrence of σ-holes on the systems under consideration with disparate magnitudes that increased according to the following order: AeF2O3 < XF3O2 < ZF5. In line with EP outcomes, the proficiency of σ-hole site-based interactions increased as the atomic size of the central atom increased with a higher favorability for the pyridine-based complexes over NCH-based ones. The interaction energy showed the most favorable negative values of -35.97, -44.53, and -56.06 kcal/mol for the XeF2O3···, IF3O2···, and SbF5···pyridine complexes, respectively. The preferentiality pattern of the studied interactions could be explained as a consequence of (i) the dramatic rearrangement of ZF5 molecules from the trigonal bipyramid geometry to the square pyramidal one, (ii) the significant and tiny deformation energy in the case of the interaction of XF3O2 molecules with pyridine and NCH, respectively, and (iii) the absence of geometrical deformation within the AeF2O3···pyridine and ···NCH complexes other than the XeF2O3···pyridine one. Quantum theory of atoms in molecules and noncovalent interaction index findings reveal the partially covalent nature of most of the investigated interactions. Symmetry-adapted perturbation theory affirmations declared that the electrostatic component was the driving force beyond the occurrence of the considered interactions. The obtained findings will help in improving our understanding of the effect of geometrical deformation on intermolecular interactions.
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Fungicidal application has been the common and prime option to combat fruit rot disease (FRD) of arecanut (Areca catechu L.) under field conditions. However, the existence of virulent pathotypes, rapid spreading ability, and improper time of fungicide application has become a serious challenge. In the present investigation, we assessed the efficacy of oomycete-specific fungicides under two approaches: (i) three fixed timings of fungicidal applications, i.e., pre-, mid-, and post-monsoon periods (EXPT1), and (ii) predefined different fruit stages, i.e., button, marble, and premature stages (EXPT2). Fungicidal efficacy in managing FRD was determined from evaluations of FRD severity, FRD incidence, and cumulative fallen nut rate (CFNR) by employing generalized linear mixed models (GLMMs). In EXPT1, all the tested fungicides reduced FRD disease levels by >65% when applied at pre- or mid-monsoon compared with untreated control, with statistical differences among fungicides and timings of application relative to infection. In EXPT2, the efficacy of fungicides was comparatively reduced when applied at predefined fruit/nut stages, with statistically non-significant differences among tested fungicides and fruit stages. A comprehensive analysis of both experiments recommends that the fungicidal application can be performed before the onset of monsoon for effective management of arecanut FRD. In conclusion, the timing of fungicidal application based on the monsoon period provides better control of FRD of arecanut than an application based on the developmental stages of fruit under field conditions.
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The problem of low efficiency of organic solar cells can be solved by improving the charge mobility and open circuit voltage of these cells. The current research aims to present the role of π-linkers, having extended conjugation, between the donor and acceptor moieties of indacenodithiophene core-based A-π-D-π-A type SJ-IC molecule to improve the photovoltaic performance of pre-existing SJ-IC. Several crucial photovoltaic parameters of SJ-IC and seven newly proposed molecules were studied using density functional theory. Surprisingly, this theoretical framework manifested that the tailoring of SJ-IC by replacing its π-linker with linkers having extended π-conjugation gives a redshift in maximum absorption coefficient in the range of 731.69-1112.86 nm in a solvent. In addition, newly designed molecules exhibited significantly narrower bandgaps (ranging from 1.33 eV to 1.93 eV) than SJ-IC having a bandgap of 2.01 eV. Similarly, newly designed molecules show significantly less excitation energy in gaseous and solvent phases than SJ-IC. Furthermore, the reorganization energies of DL1-DL7 are much lower than that of SJ-IC, indicating high charge mobility in these molecules. DL6 and DL7 have shown considerably improved open circuit voltage (VOC), reaching 1.49 eV and 1.48 eV, respectively. Thus, the modification strategy employed herein has been fruitful with productive effects, including better tuning of the energy levels, lower bandgaps, broader absorption, improved charge mobility, and increased VOC. Based on these results, it can be suggested that these newly presented molecules can be considered for practical applications in the future.
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The efficiency of pristine graphene (GN) in the delivery process of the Favipiravir (FPV) anti-COVID-19 drug was herein revealed within the FPVâ¯GN complexes in perpendicular and parallel configurations in terms of the density functional theory (DFT) method. Adsorption energy findings unveiled that the parallel configuration of FPVâ¯GN complexes showed higher desirability than the perpendicular one, giving adsorption energy up to -15.95 kcal mol-1. This favorability could be interpreted as a consequence of the contribution of π-π stacking to the overall strength of the adsorption process in the parallel configuration. Frontier molecular orbitals (FMO) findings demonstrated the ability of the GN nanosheet to adsorb the FPV drug by the alteration in the EHOMO, ELUMO, and Egap values before and after the adsorption process. Based on Bader charge results, the FPV drug and GN sheet exhibited electron-donating and -accepting characters, respectively, which was confirmed by the negative sign of the computed charge transfer (Qt) values. The FPV(R)â¯T@GN complex showed the most desirable Qt value of -0.0377e, which was in synoptic with the adsorption energy pattern. Electronic properties of GN were also altered after the adsorption of the FPV drug in both configurations, with more observable changes in the parallel one. Interestingly, the Dirac point of the GN sheet coincided with the Fermi level after the adsorption process, indicating that the adsorption process unaffected the presence of the Dirac point. The occurrence of the adsorption process was also noticed by the existence of new bands and peaks in the band structure and DOS plots, respectively. Short recovery time rendered the GN nanosheet an efficient FPV drug delivery system. The obtained findings provide new insight into the biomedical applications of the GN sheet as a promising drug delivery system.
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Graphene (GN) nanosheets have been widely exploited in biomedical applications as potential nanocarriers for various drugs due to their distinct physical and chemical properties. In this regard, the adsorption behavior of cisplatin (cisPtCl2) and some of its analogs on a GN nanosheet was investigated in perpendicular and parallel configurations by using density functional theory (DFT). According to the findings, the most significant negative adsorption energies (Eads) within the cisPtX2â¯GN complexes (where X = Cl, Br, and I) were observed for the parallel configuration, with values up to -25.67 kcal/mol at the H@GN site. Within the perpendicular configuration of the cisPtX2â¯GN complexes, three orientations were investigated for the adsorption process, namely, X/X, X/NH3, and NH3/NH3. The negative Eads values of the cisPtX2â¯GN complexes increased with the increasing atomic weight of the halogen atom. The Br@GN site showed the largest negative Eads values for the cisPtX2â¯GN complexes in the perpendicular configuration. The Bader charge transfer outcomes highlighted the electron-accepting properties of cisPtI2 within the cisPtI2â¯GN complexes in both configurations. The electron-donating character of the GN nanosheet increased as the electronegativity of the halogen atom increased. The band structure and density of state plots revealed the occurrence of the physical adsorption of the cisPtX2 on the GN nanosheet, which was indicated by the appearance of new bands and peaks. Based on the solvent effect outlines, the negative Eads values generally decreased after the adsorption process in a water medium. The recovery time results were in line with the Eads findings, where the cisPtI2 in the parallel configuration took the longest time to be desorbed from the GN nanosheet with values of 61.6 × 108 ms at 298.15 K. The findings of this study provide better insights into the utilization of GN nanosheets in drug delivery applications.
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The potentiality of the 6-mercaptopurine (MP) and 6-thioguanine (TG) expired drugs toward the corrosion inhibition of the aluminium (Al) (111) surface was widely investigated using a series of density functional theory (DFT) calculations. A competition between the anti-corrosive features of the studied drugs in the gas and aqueous phases was conducted on both neutral and protonated forms by means of quantum mechanical descriptors. The results of the electrostatic potential analysis demonstrated the prominent nucleophilic nature of the sulfur and nitrogen atoms over the structures of the examined drugs. The frontier molecular orbital theory findings outlined the higher preferability of TG over MP as a corrosion inhibitor. Upon determining the most beneficial configurations of the MP/TGâ¯Al (111) complexes, first-principles molecular dynamics simulations were executed. Interestingly, the competence of the TG drug in the corrosion inhibition process of Al (111) was more extensive than that of the MP one, which was confirmed by the interaction energy values of -1.79 and -1.64 eV, respectively. Upon obtaining the relaxed complexes, the effect of the presence of water solvent on the adsorption process was studied. These findings provide a foundation for developing green anti-corrosive inhibitors for the aluminium surface.
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An effective approach to reverse multidrug resistance (MDR) is P-glycoprotein (P-gp, ABCB1) transport inhibition. To identify such molecular regulators, the SuperNatural II database, which comprises > 326,000 compounds, was virtually screened for ABCB1 transporter inhibitors. The Lipinski rule was utilized to initially screen the SuperNatural II database, identifying 128,126 compounds. Those natural compounds were docked against the ABCB1 transporter, and those with docking scores less than zosuquidar (ZQU) inhibitor were subjected to molecular dynamics (MD) simulations. Based on MM-GBA binding energy (ΔGbinding) estimations, UMHSN00009999 and UMHSN00097206 demonstrated ΔGbinding values of -68.3 and -64.1 kcal/mol, respectively, compared to ZQU with a ΔGbinding value of -49.8 kcal/mol. For an investigation of stability, structural and energetic analyses for UMHSN00009999- and UMHSN00097206-ABCB1 complexes were performed and proved the high steadiness of these complexes throughout 100 ns MD simulations. Pharmacokinetic properties of the identified compounds were also predicted. To mimic the physiological conditions, MD simulations in POPC membrane surroundings were applied to the UMHSN00009999- and UMHSN00097206-ABCB1 complexes. These results demonstrated that UMHSN00009999 and UMHSN00097206 are promising ABCB1 inhibitors for reversing MDR in cancer and warrant additional in-vitro/in-vivo studies.
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Resistencia a Medicamentos Antineoplásicos , Simulação de Dinâmica Molecular , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos , Lipídeos/farmacologia , Simulação de Acoplamento Molecular , Linhagem Celular TumoralRESUMO
Structural aspects of molnupiravir complexed with the RNA of the SARS-CoV-2 virus have been recently resolved inside the RNA-dependent RNA polymerase (RdRp), demonstrating the interactions of molnupiravir with purine nucleosides. However, the preference of molnupiravir to interact with one purine nucleoside over another has not been clearly investigated. Herein, the complexation of molnupiravir in its active form with guanosine and adenosine was compared, using sundry density functional theory calculations. The plausible tautomeric structures of the molnupiravir drug in complex with guanosine/adenosine were minutely scrutinized. The relative energy findings outlined the favorability of amino-molnupiravir···keto-amino-guanosine and imino-molnupiravir···amino-adenosine optimized complexes. According to the interaction (Eint) and binding (Ebind) energy values, higher preferential base-pairing of molnupiravir with guanosine over the adenosine one was recognized with Eint/Ebind values of -31.16/-21.81 and -13.93/-12.83 kcal/mol, respectively. This could be interpreted by the presence of three and two hydrogen bonds within the former and latter complexes, respectively. Observable changes in the electronic properties and global indices of reactivity of the studied complexes also confirmed the preferential binding within the studied complexes. The findings from the quantum theory of atoms in molecules and the noncovalent interaction index also support the partially covalent nature of the investigated interactions. For both complexes, changes in thermodynamic parameters outlined the spontaneous, exothermic, and nonrandom states of the inspected interactions. Inspecting the solvent effect on the studied interactions outlined more observable amelioration within the water medium compared with the gas one. These results would be a durable ground for the forthcoming studies concerned with the interactions of the molnupiravir drug with purine nucleosides.
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σ-Hole and lone-pair (lp)-hole interactions of aerogen oxides with Lewis bases (LB) were comparatively inspected in terms of quantum mechanics calculations. The ZOn ⯠LB complexes (where Z = Kr and Xe, n = 1, 2, 3 and 4, and LB = NH3 and NCH) showed favourable negative interaction energies. The complexation features were explained in light of σ-hole and lp-hole interactions within optimum distances lower than the sum of the respective van der Waals radii. The emerging findings outlined that σ-hole interaction energies generally enhanced according to the following order: KrO4 ⯠< KrO⯠< KrO3⯠< KrO2â¯LB and XeO4⯠< XeO⯠< XeO2⯠< XeO3â¯LB complexes with values ranging from -2.23 to -12.84 kcal mol-1. Lp-hole interactions with values up to -5.91 kcal mol-1 were shown. Symmetry-adapted perturbation theory findings revealed the significant contributions of electrostatic forces accounting for 50-65% of the total attractive forces within most of the ZOnâ¯LB complexes. The obtained observations would be useful for the understanding of hole interactions, particularly for the aerogen oxides, with application in supramolecular chemistry and crystal engineering.