Molecular Study Research Articles

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

Molecular study of KRAS mutations in Iraqi patients with gastrointestinal tract cancer

Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2

Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2

Molecular dynamics simulation study of post‐transition state bifurcation: A case study on the ambimodal transition state of dipolar/Diels–Alder cycloaddition

AbstractThe potential energy surfaces for the reactions of 1,3‐butadiene with 2‐hydroxythioacrolein and 2‐aminoacrolein exhibit ambimodal transition states leading to both dipolar (4 + 3) and Diels–Alder (4 + 2) cycloaddition products, thereby demonstrating a post transition state bifurcation feature. We have investigated the bifurcation dynamics of these reactions using three molecular dynamics (MD) methods: quasi‐classical trajectory, classical MD, and ring‐polymer MD simulations. The trajectory calculations were performed with the semiempirical GFN2‐xTB method with the element‐specific parameters optimized to reproduce the density‐functional theory calculations. The effect of water solvation was examined using an implicit solvation model, revealing significant differences in bifurcation dynamic between gas‐phase and solution‐phase reactions. Nuclear quantum effects were found to play a crucial role in the proton‐transfer process from the (4 + 3) intermediate to the (4 + 3) product in the case of the 2‐aminoacrolein reaction.

Interaction of Norsecurinine-Type Oligomeric Alkaloids with α-Tubulin: A Molecular Docking Study.

The medicinal plant Securinega virosa (Roxb ex. Willd) Baill., also known as Flueggea virosa (Roxb. ex Willd.) Royle, is commonly used in traditional medicine in Africa and Asia for the management of diverse pathologies, such as parasite infections, diabetes, and gastrointestinal diseases. Numerous alkaloids have been isolated from the twigs and leaves of the plant, notably a variety of oligomeric indolizidine alkaloids derived from the monomers securinine and norsecurinine which both display anticancer properties. The recent discovery that securinine can bind to tubulin and inhibit microtubule assembly prompted us to investigate the potential binding of two series of alkaloids, fluevirosines A-H and fluevirosinine A-J, with the tubulin dimer by means of molecular modeling. These natural products are rare high-order alkaloids with tri-, tetra-, and pentameric norsecurinine motifs. Despite their large size (up to 2500 Å3), these alkaloids can bind easily to the large drug-binding cavity (about 4800 Å3) on α-tubulin facing the β-tubulin unit. The molecular docking analysis suggests that these hydrophobic macro-alkaloids can form stable complexes with α/β-tubulin. The tubulin-binding capacity varies depending on the alkaloid size and structure. Structure-binding relationships are discussed. The docking analysis identifies the trimer fluevirosine D, tetramer fluevirosinine D, and pentamer fluevirosinine H as the most interesting tubulin ligands in the series. This study is the first to propose a molecular target for these atypical oligomeric Securinega alkaloids.

Atomistic simulations of the interaction of edge dislocations with β-Nb precipitates in Zr-Nb alloys

Experiments have shown that precipitation can affect the mechanical properties of zirconium alloy, but the interaction mechanism between dislocations and Nb precipitates in zirconium alloys is still unclear. Thus, a systematic molecular dynamics study was performed to investigate the interaction between edge dislocations and Nb precipitates. It was found that the dislocation passed through Nb precipitate by shear mechanism or bypass mechanism of forming jogs, and the critical resolved shear stress increased with the diameter of the precipitate. After completion of the interaction, dislocations formed jogs due to climb when the precipitates were larger than 2 or 3 nm. Some atoms in the precipitate were more disordered after dislocation shearing, and dislocation fragments were generated around the precipitate, both of which lead to the precipitate hardening. The calculation of obstacle strength further confirmed that unsheared Nb precipitates until hundreds of nanometers were the weak obstacle for dislocations.

ReaxFF reactive molecular dynamic and density functional theory study on the co-pyrolysis mechanism of waste 1,1,1,2-tetrafluoroethane and waste plastics to produce high value-added chemicals and fuels

Pyrolysis is one of the potential way for the degradation of hydrofluorocarbons, but it is difficult to make effective use of the complex pyrolysis products. The addition of plastics can provide sufficient hydrogen source for the degradation of hydrofluorocarbons to generate the high value-added chemicals and fuels. Density functional theory calculation and reactive molecular dynamic simulation are employed to investigate the co-pyrolysis mechanism of 1,1,1,2-tetrafluoroethane and low-density polyethylene in this work. The results show that the H atoms provided by low-density polyethylene promote the defluorination reactions of 1,1,1,2-tetrafluoroethane to generate HF and short chain hydrocarbons, and the number of F atoms in HF molecules accounted for nearly 80 % of the whole reaction system, achieving a better defluorination effect. The defluorination rate of 1,1,1,2-tetrafluoroethane and plastics co-pyrolysis is more than 5 times that of pure 1,1,1,2-tetrafluoroethane pyrolysis. The main co-pyrolysis products of 1,1,1,2-tetrafluoroethane and low-density polyethylene are H2, HF and short chain hydrocarbons, the purpose of hydrofluorocarbons degradation into high value-added chemicals and fuels is realized in this study. This work provides a green, effective way for the conversion waste hydrofluorocarbons and waste plastics into high value-added chemicals and fuels, and achieves the conversion of waste hydrofluorocarbon refrigerants to more economical products.

Eco-friendly bio-larvicidal and antimicrobial activity of isolated bioactive compound from Kurthia gibsonii (Bacillales)

The targeted organisms include mosquito vectors, bacterial pathogens and non-targeted organisms. Preliminary mosquito larvicidal activity was conducted using cell-free supernatants (CFSs) from 11 gut bacteria. Among them, the bacterium SS11 exhibited promising results and was identified as Kurthia gibsonii based on its 16S rRNA sequence (1350 bp). The diethyl ether extract (DEE) of K. gibsonii demonstrated significant larvicidal effects, with LC50 values of 5.59 µL/mL and 8.59 µL/mL for 3rd instar larvae of Aedes aegypti and 2nd instar larvae of Anopheles stephensi, respectively. Analysis of the DEE using FT-IR, and GC-MS revealed the presence of 16 functional groups, and 7 bioactive compounds, respectively. A molecular docking study identified GC-MS compounds against odorant receptors from A. aegypti and odorant-binding proteins from A. stephensi was performed to assess the interaction and binding affinity. Overall, these findings suggest that the bioactive compounds 2, 4, 6-tribromoaniline from the DEE of K. gibsonii hold potential as an environmentally compatible alternative for biocontrol purposes, and compounds 9-tricosene and didecyl phthalate can be used for mosquito traps.

Integration of Indigenous Research Methodologies, Traditional Ecological Knowledge and molecular scatology in an assessment of mesocarnivore presence, diet and habitat use on Yurok Ancestral Lands.

Partnerships between Tribes and researchers in wildlife monitoring and application of Traditional Ecological Knowledge (TEK) have taken a variety of forms, and some scholars have noted a need for culturally sensitive approaches. Guided by Indigenous Research Methodologies, this research is coupled with Yurok TEK, or hlkelonah 'ue-megetohl ('to take care of the earth'), enabling an applied, culturally sensitive approach in partnership with the Yurok Tribe. We present results from a molecular scatology study of wildlife within the ancestral territory of the Yurok Tribe. Scats were collected opportunistically on road transects. All samples (N = 132) were analysed via DNA barcoding and results matched to documented 'Oohl 'we-toh (Yurok language) names to determine the depositor species (N = 8). Though there were four focal mesocarnivore species in our study, only bobcat (Chmuuek; Lynx rufus) and gray fox (Wergers; Urocyon cinereoargenteus) were detected as depositor species. Post hoc analyses were conducted to explore distribution, habitat use and selection in a use-availability context, and food habits of these two species. We found almost complete separation of bobcat and gray fox use of transects, as well as indication of partitioning of vegetation cover types and food. We demonstrate an integrated framework of Western and Indigenous sciences that allows the Indigenous researcher to transcend structured academic disciplinary boundaries. Our approach can be modified for partnerships between Tribes, agencies, academics and students for wildlife monitoring in broader geographic regions in various research applications.

Twinning initiation from edge dislocations pinned by hydrogen atoms in bcc iron: A molecular dynamics study

Understanding how hydrogen affects the slip and twinning behaviors in metals is paramount for ensuring safe material use in a hydrogen environment and contributing to the development of hydrogen-resistant structural metals. Despite recent reports highlighting an increase in hydrogen-induced twinning in metals under applied deformations, the root case remains elusive. Here, we use molecular dynamics simulations to investigate how high hydrogen concentrations and shear direction affect edge-dislocation behavior in bcc iron. Our findings reveal that the pinning effect increases with hydrogen density along the dislocation line. This effect becomes more pronounced when shear is applied along the twinning direction. We demonstrate the nucleation of micro-twinning, characterized by a three atomic-layer thickness, originating from the dislocation under these conditions. The growth mechanism of this phenomenon aligns with Mahajan's model. Our findings identify the high shear stress as the primary driver for twinning, owing to the hydrogen's strong pinning effect.

Mechanism of Si Ni San Combined with Astragalus in Treating Hepatic Fibrosis: A Network Pharmacology and Molecular Docking Study.

Si Ni San combined with Astragalus (SNSQ) has demonstrated significant efficacy in the treatment of hepatic fibrosis (HF), as confirmed by clinical practice. However, its pharmacological mechanism remains unclear. This study employs network pharmacology to identify key targets and proteins for molecular docking. Additionally, animal experiments were conducted to validate the network pharmacology results, providing further insights into the mechanism of SNSQ in treating HF. Effective compounds of SNSQ were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Molecular formula structures of these effective compounds were obtained from the PubChem database. Partial target proteins with a probability greater than 0.6 were sourced from the SWISS database. Uniprot IDs corresponding to these target proteins were retrieved from the SUPERPRED database. The remaining target proteins of the compounds were obtained from the Uniprot database based on the Uniprot IDs. The drug target proteins were then summarized. Target points related to HF were selected from the GeneCards and OMIM databases. Common target points were identified in the Venn diagram and imported into Cytoscape 3.9.1 software to construct the "SNSQ-effective compound-target pathway-HF" network. AutoDock software was used for molecular docking of compounds and target proteins with high-degree values. The common target points underwent GO function enrichment and KEGG pathway enrichment analysis using the DAVID database. An HF rat model was established, and serum AST and ALT activities were measured. The Hyp assay kit was utilized to detect the Hyp content in liver tissue. To the transcription levels of pro-inflammatory factors (IL-1β, TNF-α, IL-6) and anti-inflammatory factors (IL-10, TGF-β1, IL-4) in rat serum and liver.IL-1β, TNF-α, IL-10, and TGF-β1 were chosen for validation through ELISA. Western blotting and qRT-PCR were used to assess the expression of related proteins, namely NFKB1, NF-κBp65, NF-κBp50, α-SMA, and Col-1 in liver tissue. qRT-PCR was also employed to study the expression of ECM synthesis and proliferation-related genes, including Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue, as well as the inhibition of the ECM-related gene MMP13 in HSC-T6 cells and rat liver tissue. A total of 16 valid compounds were predicted, with kaempferol, sitosterol, and isorhamnetin exhibiting high-degree values. KEGG enrichment analysis revealed that the target genes of SNSQ were enriched in multiple pathological pathways, with the NF-Kappa B signaling pathway being predominant. Molecular docking simulations indicated strong affinities between SNSQ's primary components-kaempferol, sitosterol, isorhamnetin-and NFKB1. Experimental results demonstrated significant reductions in AST, ALT, and Hyp levels in the SNSQ group. Pro-inflammatory factors (IL-1β, TNF-ɑ) were markedly reduced, while anti-inflammatory factors (IL-10, TGF-β1) were substantially increased. The protein expression and transcription levels of α-SMA and Col-1 were significantly decreased, whereas those of NFKB1, NF-κBp65, and NF-κBp50 were notably elevated. mRNA expression levels of Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue were significantly decreased, whereas MMP13 mRNA expression level was significantly increased. Treatment of HF with SNSQ involves multiple targets and pathways, with a close association with the overexpression of NFKB1 and activation of the NF-Kappa B signaling pathway. Its mechanism is closely linked to the activation of inflammatory responses, HSC activation, and proliferation.

Computational Screening of Some Phytochemicals to Identify Best Modulators for Ligand Binding Domain of Estrogen Receptor Alpha.

The peculiar aim of this study is to discover and identify the most effective and potential inhibitors against the most influential target ERα receptor by in silico studies of 45 phytochemicals from six diverse ayurvedic medicinal plants. The molecular docking investigation was carried out by the genetic algorithm program of AutoDock Vina. The molecular dynamic (MD) simulation investigations were conducted using the Desmond tool of Schrödinger molecular modelling. This study identified the top ten highest binding energy phytochemicals that were taken for drug-likeness test and ADMET profile prediction with the help of the web-based server QikpropADME. Molecular docking study revealed that ellagic acid (-9.3 kcal/mol), emodin (-9.1 kcal/mol), rhein (-9.1 kcal/mol), andquercetin (-9.0 kcal/mol) phytochemicals showed similar binding affinity as standard tamoxifen towards the target protein ERα. MD studies showed that all four compounds possess comparatively stable ligand-protein complexes with ERα target compared to the tamoxifen-ERα complex. Among the four compounds, phytochemical rhein formed a more stable complex than standard tamoxifen. ADMET studies for the top ten highest binding energy phytochemicals showed a better safety profile. Additionally, these compounds are being reported for the first time in this study as possible inhibitors of ERα for treating breast cancer, according to the notion of drug repurposing. Hence, these phytochemicals can be further studied and used as a parent core molecule to develop innovative lead molecules for breast cancer therapy.

Oblique impingement of binary droplets at the nanoscale on superhydrophobic surfaces: A molecular dynamics study.

The impacting phenomenon of nanodroplets has received much attention due to their importance in various industrial applications. The oblique impingement of single droplets is well understood; however, the effect of oblique angle on impacting the dynamics of multiple droplets at the nanoscale is very limited. To address this gap, we perform molecular dynamics (MD) simulations to study the impacting dynamics of binary nanodroplets with various oblique angles (αob) and Weber numbers (We). Using MD simulations, we directly capture the detailed morphological evolution of the impacting binary droplets with various given conditions. Compared to the oblique impingement of a single droplet, the evolution of impacting binary droplets involves two novel dynamic characteristics: the asymmetric dynamics with droplet preferential spreading in the y direction and the rotating of the coalescing droplet. The mechanisms underlying are well studied. The asymmetric dynamics is a result of the velocity gradient of the outer edge of the spreading droplet, and the rotating effect is due to the change in angular momentum induced by surface force. The analysis and study of these phenomena have never been mentioned in previous studies of single droplet. Finally, we investigate the effect of αob and We on normalized moving distance (L/Dsin) and contact time (tc). This work paves the way for offering a comprehensive understanding of the oblique impingement of binary nanodroplets.

Design, synthesis and molecular docking study of novel triazole–quinazolinone hybrids as antimalarial and antitubercular agents

In a quest to discover new antimalarial and antitubercular drugs, we have designed and synthesized a series of novel triazole–quinazolinone hybrids. The in vitro screening of the triazole–quinazolinone hybrid entities against the plasmodium species P. falciparum offered potent antimalarial molecules 6c, 6d, 6f, 6g, 6j &6k owing comparable activity to the reference drugs. Furthermore, the target compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB) H37Rv strain. Among the screened compounds, 6c, 6d and 6l were found to be the most active molecules with a MIC values of 19.57–40.68 μM. The cytotoxicity of the most active compounds was studied against RAW 264.7 cell line by MTT assay and no toxicity was observed. The computational study including drug likeness and ADMET profiling, DFT, and molecular docking study was done to explore the features of target molecules. The compounds 6a, 6g, and 6k exhibited highest binding affinity of −10.3 kcal/mol with docked molecular targets from M. tuberculosis. Molecular docking study indicates that all the molecules are binding to the falcipain 2 protease (PDB: 6SSZ) of the P. falciparum. Our findings indicated that these new triazole–quinazolinone hybrids may be considered hit molecules for further optimization studies.

Chemical Constituents, Antioxidant, and Antimicrobial Activities of Ethyl Acetate Fractionated Extract from Rhizomes of Zingiber monophyllum Gagnep.: In vitro and in silico Screenings

Objective/Background: Zingiber monophyllum Gagnep., a member of the Zingiberaceae family, is known for its significant biological activities. The current study aimed to determine the volatile components of the ethyl acetate (EtOAc) fractionated extract found in the rhizomes of this species. This is the first report on the chemical composition and bioactivities of Z. monophyllum rhizomes fractionated extract. Methods: The chemical constituents were analyzed and determined using gas chromatography-mass spectrometry (GC-MS). Antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) assays using ascorbic acid as a positive control. Antibacterial and antifungal properties of the EtOAc fractionated extract of Z. monophyllum rhizomes were assessed against Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus, and Candida albicans. Density functional theory (DFT) and molecular docking were also employed to illustrate antioxidant and antimicrobial activities. Results: Nine components were identified by GC-MS analysis from the EtOAc fractionated extract of Z. monophyllum rhizomes. ( E)-labda-8(17),12-diene-15,16-dial (9), spathulenol (2), and neointermedeol (5) were the major components (21.8%, 16.8%, and 11.9%, respectively). Moderate antioxidant activities of the EtOAc fractionated extract were observed via both the DPPH assay and the FRAP assay using ascorbic acid as the standard compound. The extract demonstrated remarkable antimicrobial activity against all examined microbial strains, except for P. aeruginosa. The DFT study analyzed the antioxidant potential of each component in the fractionated extract. Molecular docking study chose E. faecalis DNA gyrase B, E. coli DNA gyrase B, S. aureus biotin protein ligase, E. faecalis Alanine racemase, and C. albicans N-myristoyltransferase as potential target proteins for antimicrobial activity. Conclusion: In this study, the chemical composition of the EtOAc fractionated extract of Z monophyllum rhizomes was demonstrated through GC-MS analysis for the first time. Nine components, including alloaromadendrene, spathulenol, globulol, τ-cadinol, neointermedeol, aromadendrene oxide-(2), ambrial, (E)-15,16-dinorlabda-8(17),11-dien-13-one, and (E)-lambda-8 (17),12-diene-15,16-dial along with relative content were identified in this fractionated extract. The bioassays revealed that the fractionated extract showed moderate antioxidant activities and significant antimicrobial activities. The antioxidant and antimicrobial potential of each component was also theoretically examined by the DFT study and molecular docking study, respectively.

Novel quinazolin-2-yl 1,2,3-triazole hybrids as promising multi-target anticancer agents: Design, synthesis, and molecular docking study

In our study, a series of quinazoline-1,2,3-triazole hybrids (14a-r) have been designed and synthesized as multi-target EGFR, VEGFR-2, and Topo II inhibitors. All synthesized hybrids were assessed for their anticancer capacity. MTT assay revealed that compounds 14a, 14d, and 14k were the most potent hybrids against four cancer cell lines, HeLa, HePG-2, MCF-7, and HCT-116 at low micromolar range while exhibiting good selectivity against normal cell line WI-38. Sequentially, the three compounds were evaluated for EGFR, VEGFR-2, and Topo II inhibition. Compound 14d was moderate EGFR inhibitor (IC50 0.103 µM) compared to Erlotinib (IC50 0.049 µM), good VEGFR-2 inhibitor (IC50 0.069 µM) compared to Sorafenib (IC50 0.031 µM), and stronger Topo II inhibitor (IC50 19.74 µM) compared to Etoposide (IC50 34.19 µM) by about 1.7 folds. Compounds 14k and 14a represented strong inhibitory activity against Topo II with (IC50 31.02 µM and 56.3 µM) respectively, compared to Etoposide. Additionally, cell cycle analysis and apoptotic induction were performed. Compound 14d arrested the cell cycle on HeLa at G2/M phase by 17.53 % and enhanced apoptosis by 44.08 %. A molecular Docking study was implemented on the three hybrids and showed proper binding interaction with EGFR, VEGFR-2, and Topo II active sites.

Novel 10,11-Dihydro-5H-dibenzo[b,f]azepine Triazoles Hybrids: Synthesis, in vitro Antioxidant activity and Xanthine oxidase inhibition and Computational study

The study reports the synthesis and antioxidant capability of six novel 10,11-dihydro-5H-dibenzo[b,f]azepine linked 1,2,3-triazoles 6(a–f), synthesized in good yield using copper (II)-catalyzed azide-alkyne 1,3- dipolar cycloaddition reaction (Click Chemistry) under ultrasonication. The alkyne of 10,11-dihydro-5H-dibenzo[b,f]azepine has been prepared and confirmed to have monoclinic geometry using single crystal XRD. All the synthesized compounds are fully characterized using 1H and 13C-NMR, IR, and HRMS. The new compounds 6(a-f) were studied for in vitro DPPH and FRAP antioxidant assay, as well as their ability to inhibit xanthine oxidase enzyme. Compound 6d showed minimum IC50 values of 3.58 ±1.5 µg/ml and 58.66±3 µM for DPPH and FRAP inhibitory effect respectively. The HAT (hydrogen atom transfer) mechanism for DPPH activity and SET (single electron transfer) mechanism for FRAP activity of compound 6d, has been studied through a DFT study on B3LYP hybrid functional at 6-31+G(d,p) basis set. The bond dissociation enthalpy and ionization potential of 6d are 77.01 kcal/mol and 162.59 kcal/mol respectively, proving it to be an excellent antioxidant. Being the best antioxidant 6d has been further used for in vitro inhibition study on xanthine oxidase enzyme isolated from buttermilk. 6d derivative has an IC50 value of 4.93±2 µg/ml much lesser than the standard drug Allopurinol, having an IC50 value of 10.29±1 µg/ml. The molecular docking study is performed on 6(a-f) for XO protein PDBID:1FIQ. All compounds showed effective binding with XO enzyme and the best lead 6d showed a maximum binding energy value of -10.0 kcal/mol. A molecular dynamic simulation study of 100 ns further proved the stability of enzyme 6d complex in the biological system.

Phenolic enriched fraction of Clerodendrum glandulosum Lindl. leaf extract ameliorates hyperglycemia and oxidative stress in streptozotocin-nicotinamide induced diabetic rats

BackgroundClerodendrum glandulosum Lindl. is an important ethnomedicinal shrub of Northeast India, used by traditional healers to control various ailments like diabetes, hypertension, arthritis, etc. ObjectivesThe present study was conducted to explore the anti-hyperglycemic and antioxidative effects of the polyphenol-rich fraction (PRF) of C. glandulosum leaf extract and identification of its major bioactive compounds. Further, an in-silico molecular docking study was also performed to understand the molecular interactions of the identified major compounds with some target proteins associated with diabetic complications. Materials and methodsPRF was purified from the hydromethanolic (80% MeOH) extract of leaves and subjected to assessment of in-vitro antioxidant and anti-diabetic properties. It was also subjected to evaluate the ameliorative effect during streptozotocin-nicotinamide-induced hyperglycemia in Wistar albino rats. An in-silico molecular docking study was also performed to complement the in-vitro/in-vivo studies. ResultsChemical analysis of PRF showed the presence of phenolics like caffeic acid, verbascoside, isoverbascoside, and apigenin, of which verbascoside (598.14 ± 1.24 mg/g) was found to be the principal compound. In-vitro studies showed potent antioxidant (IC50 of DPPH:32.45 ± 2.16 μg/mL; ABTS:39.08 ± 0.53 μg/mL) properties and excellent aldose reductase inhibition potential (IC50 2.18 ± 0.10 μg/mL). Treatment with PRF showed reduced blood glucose levels and increased plasma insulin levels. The results also indicate an improvement of endogenous antioxidants and suppression of inflammatory cytokines (IL-6 and TNF-α) comparable to the standard. Molecular docking studies predicted promising interactions between the identified molecules and the crucial amino acid residues of the enzymes involved in the development of hyperglycemia. ConclusionThis study revealed the antihyperglycemic and antioxidant potential of partially purified fraction PRF of C. glandulosum leaves.

Molecular Docking and Dynamics Study of Acetogenins Targeting Cyclin-dependent Kinase and In vitro Evaluation of Annona Muricata Fruit Extracts using MDA-MB-231 Breast Cancer Cell Line

Background: Overexpressed CDK1 and CDK2 are targeted as potential sites for cancer treatment. Annona muricata fruit has been reported to have more than 100 acetogenins showing cytotoxic activities against cancer cell lines. Hence the study aims to demonstrate the cytotoxicity of ethyl acetate fruit extract, its role in cell cycle progression, and apoptosis using the MDMBA-231 breast cancer cell line. Docking, dynamics, and ADME studies were also demonstrated to generate lead molecules of AM fruit responsible for cancer treatment. Method: Cell viability was quantified by the MTT assay. Cell cycle arrest and apoptotic cells were determined by flow cytometry and PI annexin V-FITC staining by flow cytometry, respectively. Molecular docking, molecular dynamics, and ADME properties of 11 acetogenins were studied using the schrödinger maestro suite 2018-1. Results: The MTT assay revealed IC50 232.9μg/ml with a high degree of cytotoxicity. The extract effectively caused cell cycle arrest at the G2M and S phases; early and late apoptosis was induced at 160 μg/ml and 320 μg/ml. Docking scores of muricin L, J, and annomuricin A complexed with CDK2 and muricin J, K, and L with CDK1 binding energy ranging is mentioned as a molecular dynamic study envisaged muricin j against CDK2 stable hydrogen and hydrophobic interactions with critical residues like ASP-86, GLN-131, HIS-84, LYS-89, PHE80, PHE82, and PHE83 throughout 200 ns (hinge region). ADMET profiling also confirmed that all 11 ligands passed the rule of 5 and 3. The in vitro and in silico studies revealed that these acetogenins could be CDK1 and CDK2 inhibitors for cancer treatment. Conclusion: The in vitro studies presume that the ethyl acetate fruit extract of AM is an excellent cytotoxic agent. In silico studies demonstrated that muricin j could lead molecules to target kinase proteins responsible for cell proliferation. ADME study enlightened us to take 11 acetogenins for the drug discovery process in managing cancer treatment.

Addressing the interaction of stem bromelain with different anionic surfactants, below, at and above the critical micelle concentration (cmc) in phosphate buffer at pH 7: Physicochemical, spectroscopic, & molecular docking study

The structural stability and therapeutic activity of Stem Bromelain (BM) have been explored by unravelling the interaction of stem BM in presence of two different types of anionic surfactants namely, bile salts, NaC and NaDC and the conventional anionic surfactants, SDDS and SDBS, below, at and above the critical micelle concentration (cmc) in aqueous phosphate buffer of pH 7. Different physicochemical parameters like, surface excess (Γcmc), minimum area of surfactants at air water interface (Amin) etc. are calculated from tensiometry both in absence and presence of BM. Several inflection points (C1, C2 and C3) have been found in tensiometry profile of surfactants in presence of BM due to the conformational change of BM assisted by surfactants. Similar observation also found in isothermal titration calorimetry (ITC) profiles where the enthalpy of micellization (ΔH0obs) of surfactants in absence and presence of BM have calculated. Further, steady state absorption and fluorescence spectra monitoring the tryptophan (Trp) emission of free BM and in presence of all the surfactants at three different temperatures (288.15 K, 298.15 K, and 308.15 K) reveal the nature of fluorescence quenching of BM in presence of bile salts/surfactants. Time resolved fluorescence studies at room temperature also support to determine the several quenching parameters. The binding constant (Kb) of BM with all the surfactants and free energy of binding (∆G0 of bile salts/surfactants with BM at different temperatures have been calculated exploiting steady state fluorescence technique. It is observed that, the binding of NaC with BM is greater as compared to other surfactants while Stern-Volmer quenching constant (KSV) is found greater in presence of SDBS as compared with others which supports the surface tension and ITC data with the fact that surface activity of surfactant(s) is decreasing with the binding of the surfactants at the core or binding pocket of BM. Circular Dichroism (CD) study shows the stability of secondary structure of BM in presence of NaC and NaDC below C3, while BM lost its structural stability even at very low surfactant concentration of SDDS and SDBS which also supports the more involvement of bile salts in binding rather than surfactants. The molecular docking studies have also been substantiated for better understanding the several experimental investigations interaction of BM with the bile salts/surfactants.

Wetting and interfacial behavior of aqueous Deep eutectic solvents on Graphite, silica and calcite surfaces: Molecular dynamics study

Understanding the wetting behavior of liquids/fluids on solid surfaces at the nanoscale can help develop more effective and efficient technologies in various applications, including microfluidics, biomedical, enhanced oil recovery, and many others. Deep eutectic solvents (DESs) have recently gained attention due to their physical and chemical properties and tunability, making them useful in many applications. This article reports the investigation of the wetting behavior of aqueous deep eutectic solvent (DES) on graphite, silicon dioxide (SiO2), and calcite (CaCO3) using molecular dynamics (MD) simulation. The study's main objective is to understand the interfacial behavior of aqueous DES on these surfaces. In the current study, two different DESs, choline-chloride (ChCl) as hydrogen bond acceptor (HBA) and two different hydrogen bond donors (HBD), urea (U) and ethylene glycol (EG) with molar ratio 1:2are used. Aqueous DES has been studied for three different concentrations of10, 20, and 30 wt% of DES molecules to explore the effect of concentration.AqueousDES system on the graphite makes a finite contact angle for all concentrations of DES.In contrast, for SiO2 and CaCO3, droplets spread and attain a contact angle below ∼ 10° due to high hydrophilicity. We confirmed that our simulation had attained equilibrium by computing the interaction energy with the substrate and system molecules. The wetting behavior of aqueous DES thin film on the surfaceis characterizedby a density profile along the z-axis (normal to the surface). Furthermore, hydrogen bond (HB) analysisis performedto elucidate the structural relationship of these aqueous-DES systems. Overall, this study provides insights into the wetting behavior of nanodroplets/film of aqueous DES on different surfaces and illustrates the structural characteristics of these systems through various properties such as contact angle, density profiles, and hydrogen bonds.