In-silico Studies Research Articles

Therapeutic potential of oleanolic acid in modulation of PI3K/Akt/mTOR/STAT-3/GSK-3β signaling pathways and neuroprotection against methylmercury-induced neurodegeneration

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that gradually deteriorates motor neurons, leading to demyelination, muscle weakness, and eventually respiratory failure. The disease involves several pathological processes, such as increased glutamate levels, mitochondrial dysfunction, and persistent neuroinflammation, often exacerbated by environmental toxins like mercury. This study explores the therapeutic potential of Olea europaea active phytoconstituents oleanolic acid (OLA) against ALS by targeting the overactivated PI3K/Akt/mTOR/STAT-3/GSK-3β signalling pathways. Methods involved in-silico studies, in vitro and in vivo experiments in which varying doses of methylmercury 5 mg/kg, p.o. and OLA (100 and 200 mg/kg, i.p.) were administered to rats for 42 days. Behavioural assessments, gross morphological, histopathological, and neurochemical parameters were measured in cerebrospinal fluid (CSF), blood plasma, and brain homogenates (cerebral cortex, hippocampus, striatum, midbrain, cerebellum) along with complete blood count (CBC) analysis. Results revealed OLA's significant neuroprotective properties. OLA effectively modulated targeted pathways, reducing pro-inflammatory cytokines, restoring normal levels of myelin basic protein (MBP) and neurofilament light chain (NEFL), and reducing histopathological changes. Gross pathological studies indicated less tissue damage, while CBC analysis showed improved hematology parameters. Additionally, the combination of OLA and edaravone (10 mg/kg, i.p.) demonstrated enhanced efficacy, improving motor functions and extending survival in ALS model rats. In conclusion, OLA exhibits significant therapeutic potential for ALS, acting as a potent modulator of key pathological signaling pathways. The findings suggest the feasibility of integrating OLA into existing treatment regimens, potentially improving clinical outcomes for ALS patients. However, further research must validate these findings in human clinical trials.

Non-invasive regional parameter identification of degenerated human meniscus

Accurate identification of local changes in the biomechanical properties of the normal and degenerative meniscus is critical to better understand knee joint osteoarthritis onset and progression. Ex-vivo material characterization is typically performed on specimens obtained from different locations, compromising the tissue's structural integrity and thus altering its mechanical behavior. Therefore, the aim of this in-silico study was to establish a non-invasive method to determine the region-specific material properties of the degenerated human meniscus. In a previous experimental magnetic resonance imaging (MRI) study, the spatial displacement of the meniscus and its root attachments in mildly degenerated (n = 12) and severely degenerated (n = 12) cadaveric knee joints was determined under controlled subject-specific axial joint loading. To simulate the experimental response of the lateral and medial menisci, individual finite element models were created utilizing a transverse isotropic hyper-poroelastic constitutive material formulation. The superficial displacements were applied to the individual models to calculate the femoral reaction force in an inverse finite element analysis. During particle swarm optimization, the four most sensitive material parameters were varied to minimize the error between the femoral reaction force and the force applied in the MRI loading experiment. Individual global and regional parameter sets were identified. In addition to in-depth model verification, prediction errors were determined to quantify the reliability of the identified parameter sets. Both compressibility of the solid meniscus matrix (+141 %, p ≤ 0.04) and hydraulic permeability (+53 %, p ≤ 0.04) were significantly increased in the menisci of severely degenerated knees compared to mildly degenerated knees, irrespective of the meniscus region. By contrast, tensile and shear properties were unaffected by progressive knee joint degeneration. Overall, the optimization procedure resulted in reliable and robust parameter sets, as evidenced by mean prediction errors of <1 %. In conclusion, the proposed approach demonstrated high potential for application in clinical practice, where it might provide a non-invasive diagnostic tool for the early detection of osteoarthritic changes within the knee joint.

Antibacterial and Antibiofilm potential of Thuja orientalis L. extract targeting cariogenic Enterococcus faecalis ATCC 29212: A combined in-vitro, in-silico study, and cytotoxicity screening

ObjectivesIn this study, we explored the efficacy of methanolic extract of Thuja orientalis (TOME) as a novel antibacterial and antibiofilm agent against a cariogenic bacterium, Enterococcus faecalis ATCC 29212. DesignAntibacterial susceptibility studies were conducted and surface morphology analysis was performed using field emission scanning electron microscopy (FESEM). Antibiofilm activity was evaluated through both qualitative and quantitative biofilm inhibition assays and validated by microscopic analysis. In-silico molecular docking studies were conducted using the EDock server. The effectiveness of TOME was substantiated by biofilm model on dentin discs and cytotoxicity towards the HaCaT cell line was assessed using the MTT assay. ResultsTOME exhibited significant bactericidal activity with minimum inhibitory concentration of 12.5mg/mL and additionally, it effectively compromised bacterial cell wall integrity. Qualitative, quantitative and microscopic studies depicted the inhibition of biofilm formation. TOME significantly impacted the production of extracellular polymeric substance and extracellular DNA. Molecular docking studies identified beta-caryophyllene as a potent inhibitor of the Enterococcal surface protein (Esp). Biofilm model depicted the reduction of bacterial load on dentin discs. Additionally, TOME showed reduced cytotoxicity on HaCaT cells, indicating its potential as a safe therapeutic agent. ConclusionThese findings highlight TOME's promise for developing novel treatments for dental infections and biofilm-associated diseases. Further research should focus on isolating and characterizing the active compounds within TOME, particularly beta-caryophyllene, to elucidate their precise mechanisms of action.

Prolonged Skin Retention of Luliconazole from SLNs Based Topical Gel Formulation Contributing to Ameliorated Antifungal Activity.

The development of effective therapy is necessary because the patients have to contend with long-termtherapy as skin fungal infections usually relapse and are hardly treated. Despite being a potent antifungal agent, luliconazole (LCZ) has certainshortcomings such as limited skin penetration, low solubility in aqueous medium, and poor skin retention. Solid Lipid Nanoparticles (SLNs) were developed using biodegradable lipids by solvent injection method and were embodied into the gel base for topical administration. After in-vitro characterizations of the formulations, molecular interactions of the drug with excipients were analyzed using in-silico studies. Ex-vivo release was determined in contrast to the pure LCZ and the commercial formulation followed by in-vivo skin localization, skin irritation index, and antifungal activity. The prepared SLNs have an average particle size of 290.7nm with no aggregation of particles and homogenous gels containing SLNs with ideal rheology and smooth texture properties were successfully prepared. The ex-vivo LCZ release from the SLN gel was lower than the commercial formulation whereas its skin deposition and skin retention were higher as accessed by CLSM studies. The drug reaching the systemic circulation and the skin irritation potential were found to be negligible. Thesolubility and drug retention in the skin were both enhanced by the development of SLNs as a carrier. Thus, SLNs offer significant advantages by delivering long lasting concentrations of LCZ at the site of infection for a complete cure of the fungal load together with skin localization of the topical antifungal drug.

Synthesis, and In-silico Studies of Indole-chalcone Derivatives Targeting Estrogen Receptor Alpha (ER-α) for Breast Cancer.

Breast cancer is the prominent reason of death in women worldwide, and the cases are increasing day by day. There are many FDA-approved drugs for treating breast cancer. Due to drug resistance, and problems in selectivity, there is a need to develop more effective agents with few side effects. Indole derivatives have demonstrated significant pharmacological potential as anti-breast cancer agents. Further, chalcone derivatives incorporating heterocyclic scaffolds play a significant role in medicine. Indole-chalcone-based compounds offer the potential for improved biological activity and enhanced drug-like properties. It prompted us to explore the synthesis of Indole-Chalcone derivatives targeting estrogen receptor alpha (ER-α) to discover potent anti-breast cancer agents. To synthesize indole-chalcone derivatives and study their binding interactions for ER-α protein by molecular docking for breast cancer treatment. In this study, indole-chalcone derivatives have been synthesized using conventional heating. With the help of Schrodinger software, molecular interaction as well as ADME (Adsorption, Distribution, Metabolism, and Excretion) studies of the compounds were conducted. Among all the synthesized compounds, four compounds (1, 2, 3, and 4) showed better docking scores (-10.24 kcal/mol, -10.15 kcal/mol, -9.40 kcal/mol, -9.29 kcal/mol, respectively) than the standard tamoxifen (-8.43 kcal/mol). From In-silico studies, we can conclude that four compounds from the synthesized series fit into the active site of ER-α. ADME properties of synthesized derivatives were found in the acceptable range. In the future, these compounds can be further explored for biological activity.

Synthesis of new multi-functionalized Schiff base derivatives based on vanillic acid: Antimicrobial activity, photophysical, DFT calculations and in-silico study

The paper reports the synthesis of novel multi-functional Schiff base derivatives (S1-S7) via Steglich esterification, thoroughly characterized by standard spectroscopic methods (1H NMR, 13C NMR, FT-IR and Mass spectrometry) and elemental analysis technique. Density Functional Theory calculations (including FMOs’, MEP, IR and UV–Visible), photophysical, molecular docking simulations, and in-vitro antimicrobial assays were employed to study the structure and reactivity of synthesized compounds. The study highlights significant antimicrobial activity of certain derivatives, which aligns with computational predictions. UV–Visible study identifies various transitions like π→π*, n→π* occurring in the system aligning with the theoretical absorption spectra. Biological studies reveal that compounds S1, S2 and S5 exhibit significant potency for antimicrobial investigation correlating with the computational study. Further, the calculated HOMO-LUMO band gap for S1-S7 molecules (3.29 eV) suggest their insulating nature. Notably, MEP study shows negative electrostatic potential near nitro group and the positive potential near alkyl groups indicating preferable site for electrophilic and nucleophilic attack, respectively. Moreover, molecular docking was implemented to computationally screen the multi-functionalized Schiff base along with molecular dynamics simulation including MM-PBSA energy calculation in order to discover the reasonable physiological significance ensuring stability of binding interactions of relevant molecules.

Exploring the cyclization of thiosemicarbazone to 1,3,4-thiadiazole: Synthesis, characterization and in-silico study

Breast cancer remains a significant health concern worldwide, necessitating the development of novel therapeutic strategies. In this study, we focus on the design, synthesis, and evaluation of isophorone-1,3,4-thiadiazoles as potential inhibitors targeting AKT1 and STAT3, crucial players in breast cancer progression. The synthesized compounds were rigorously characterized using High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy, encompassing both 1H and 13C spectra. Subsequently, Network pharmacology analysis facilitated for the identification of key genes and pathways associated with breast cancer, thereby identifying AKT1 and STAT3 as promising therapeutic targets for the designed compounds. Furthermore, the top two targets, AKT1 and STAT3, were chosen for molecular docking analyses to forecast the binding affinity of the ligands with the proteins, revealing favorable interactions between compounds 8a-c and these targets. Molecular dynamics was performed for 100 ns simulation to predict the stability of the compounds. Acceptable RMSD and RMSF values for amino acid residues indicated structural integrity and a stable protein-ligand interaction. Additionally, all designed compounds displayed favorable physicochemical properties and promising ADMET profiles. These 8a and 8c considered as promising leads for targeting AKT1 and STAT3.

Maximizing similarity: using correlation coefficients to calibrate kinetic parameters in population balance models

Crystallization plays a crucial role as a separation and purification technique, particularly in the chemical and pharmaceutical industries. By adjusting process parameters, the productivity, product quality, and efficiency of downstream processes can be improved. In complex processes, model-based design becomes invaluable. Population Balance Models (PBMs) have successfully aided the chemical industry in achieving more effective production processes for decades. These models can utilize various input data sources to identify the dominant mechanisms and calibrate model parameters. While inline particle monitoring tools serve as excellent qualitative descriptors, challenges arise from experimentation and data interpretation, hindering their direct application in the kinetic parameter estimation of PBMs. In this study, we present a novel approach that utilizes information from inline particle monitoring tools for the kinetic parameter estimation of PBMs, bypassing the associated obstacles. Our pioneering approach relies on offline product size data and the correlation-based utilization of inline particle monitoring information. The paper compares this novel strategy with two parameter estimation techniques: the classical method using solute concentration and product size data and a somewhat naïve approach, which assumes that the inline particle monitoring data can directly be compared with the simulations. The prediction capabilities are evaluated through two in-silico case studies. The results indicate that the precision and predictive capability of the correlation-based technique are comparable to the classical approach, both for noisy data and for a system undergoing significant agglomeration and deagglomeration. The use of Pearson’s correlation coefficient yields the best results in the novel cases. These findings in in-silico datasets provide a foundation and motivation for the practical application of this idea, unleashing the so-far hidden model development potential of such measurements.

Characterization and kinetics of a cathepsin B-inhibiting protein from Musa acuminata Colla peel

Hyperexpression of cathepsin B caused by an imbalance of endogenous inhibitors is involved in multiple pathologies, hence making it a key therapeutic target. Protease inhibitors are effective biomolecules that regulate protease activities and are considered potential therapeutic agents in various diseases. Plant protease inhibitors have been reported as an effective complementary alternative drug. A proteinaceous cathepsin B inhibitor (CBI-BP) has been isolated from Musa acuminata Colla (banana) peel with a molecular weight of 27.9 kDa on SDS-PAGE. The purity of the CBI-BP was confirmed on the native- PAGE. The isolated CBI-BP showed an IC50 value of 8.14 μg and a Ki value of 10.59 μg (0.19 μM). Cathepsin B inhibition kinetics indicated that CBI-BP follows a mixed-type of cathepsin B inhibition. Its inhibition activity was also confirmed by reverse zymography. The inhibitor was stable from pH 2.6 - 10.0 with maximum activity at pH 7.2, temperature 25-100°C and exhibited thermostability for 60 min at 70°C. MALDI/TOF/MS analysis of CBI-BP showed 40% similarity to the GH18 domain-containing protein (A0A4S8JRM9) from Musa balbisiana. Although in-silico docking studies showed binding of A0A4S8JRM9 to cathepsin B affects the binding energy of the substrate to cathepsin B but is not reported for any anti-cathepsin B activity. This suggests that isolated CBI-BP might be a novel protein with anti-cathepsin B activity. Thus the isolated CBI-BP may be further explored as possible anti-cathepsin B drug.

Enhanced antibacterial effect of natural tannin stabilized silver nano particles against human pathogens: A target toward FtsZ proteins

BackgroundTannins are the polyphenolic group of plant compounds having strong antimicrobial potential. Research on human pathogens using silver nanoparticles for antimicrobial purposes has opened up new possibilities in nanomedicine. ObjectiveThe present study was concerned with combining the effectiveness of the two by the green synthesis of silver nanoparticles with plant tannin. MethodsSynthesis of silver nanoparticles was done based on the tannin content of the selected plants. Characterization of the synthesized nanoparticles has been performed through UV–VIS, FTIR spectroscopy, Zeta potential, XRD analysis and FEGSEM imaging. The antibacterial potentiality of the nanoparticles was checked against two most susceptible bacteria Staphylococcus epidermidis and Salmonella typhi. ResultsAmong the studied plants, Phyllanthus emblica showed highest tannin content and best bactericidal properties. The nanoparticles synthesized with P. emblica showed the highest zone of inhibition against the studied bacteria. An in-silico comparative molecular docking study of the bioactive compounds from the selected plants was performed against the FtsZ protein of S. epidermidis and YfdX protein of S. typhi. Three compounds namely Isocorilagin,1(β), 6-di-o-galloylglucose and Hamamelitannin appeared as the best inhibitors of the said proteins and among them, Isocorilagin, a natural tannin showed the best docking score of -10.2 Kcal/mol with FtsZ protein. Further molecular dynamics simulation studies of the FtsZ protein-Isocorilagin complex support its stability indicating Isocorilagin as the natural inhibitor of the pathogenic bacterial protein FtsZ. ConclusionThese results concluded that synthesis of nanoparticles with plant tannin is a cost effective green approach and the synthesised nanoparticles appear as efficient antimicrobial agent.

Phytochemistry, antioxidant and anti-diabetic activities of Sterculia villosa in-vitro

ObjectiveAs ongoing research continues, many antidiabetic agents still have many side effects which is the reason why more and more people resort to traditional medicines such as Traditional Chinese Medicine (TCM). There are many Therapeutic Species of Sterculia spp. that are commonly used in TCM practices. Here, we have studied one of such TCM herbal plants, namely Sterculia villosa Roxb. (Chinese: 绒毛苹婆), for its antidiabetic potential. In this way, the study intends to assess its effectiveness and examine its suitability as a raw natural medicine for diabetes management in traditional medicine. MethodIn-vitro anti-diabetic property was evaluated by α-amylase and α-glucosidase enzyme inhibition and glucose uptake assays. Metabolomic profiling by GC-MS was conducted to determine the probable phyto-constituents in S. villosa. These phyto-compounds were further subjected to in-silico molecular docking studies, identifying stigmasterol as the most potent anti-diabetic phyto-compound. Glucose uptake efficacy was estimated by a fluorescence microplate reader employing glucose analog 2-NBDG. Molecular dynamic studies (MDS) were carried out with GROMACS to comprehend the protein-ligand binding stability. ResultsStigmasterol showed enhanced enzyme inhibition for both α-amylase (IC50 23.84±1.37 μM) and α-glucosidase (IC50 39.56±1.5 μM). Line-weaver Burk plot revealed competitive and mixed modes of inhibition for α-amylase and α-glucosidase, respectively. The GC-MS analysis identified 23 vital phyto-compounds present in the methanolic extract of the S. villosa leaves. Upon screening against crucial anti-diabetic proteins by in-silico molecular docking, stigmasterol followed by lupeol, Stigmasta-3,5-diene, and γ-sitosterol were found to be the most effective lead compounds. Stigmasterol also showed potent hypoglycaemic efficacy, as evidenced by augmentation of 2-NBDG glucose uptake in 3T3-L1 cells. The docking and simulation studies against four crucial anti-diabetic targets, α-amylase, α-glucosidase, GLUT 4, and IRS-1, predicted that stigmasterol exhibits a multi-pronged anti-diabetic activity mediated by α-amylase inhibition and activation of IRS1 pathway, simultaneously. The MDS studies highlighted that stigmasterol showed stable interactions with these four proteins, as evidenced by the RMSD, RMSF and hydrogen bond analysis. ConclusionThe results of this study are intriguing, as they identify stigmasterol, sourced from the medicinal plant S. villosa, as a potential breakthrough in the field of diabetic remediation. This discovery paves the way for further research and development of stigmasterol as a more effective and safer treatment for diabetes.

Exploring the utility of complementary separations in liquid chromatography

An alternative strategy is explored for the separation of samples by liquid chromatography (LC). Unlike traditional approaches that aim to resolve all components in a given sample within a single LC separation, the proposed strategy uses two or more distinct separations carried out with a different gradient program and/or using different separation chemistries i.e., a different set of mobile and stationary phase. This set of complementary incomplete separations (CIS) is selected such that each component is at least fully resolved once, meaning the most critical pairs of each individual separation can be left unseparated. This allows for a significant time saving per separation. To investigate whether such an approach can lead to overall shorter analysis times than is possible with the fastest single-run gradient separation, a comprehensive in-silico study covering a statistically significant number of samples is undertaken. The investigation shows that, for the presently considered sample sets and chemistries, CIS has a substantially higher probability, about two times greater for the simplest samples considered in this work and as much as 30 times greater for more complex samples, to fully resolve an unknown sample compared to a single gradient separation. Comparing separation speeds, the CIS approach can achieve complete sample resolution on average approximately four times faster than a single separation. Our findings thus demonstrate the potential of CIS in enhancing separation efficiency and offer insights regarding their use for solving analytical challenges.

Cofactor F420 tail length distribution in different environmental samples

Cofactor F420 is an electron carrier playing a crucial role in a variety of microorganisms during redox reactions of the primary and secondary metabolism due to its low redox potential and thus arouses increasing interest. In this study, cofactor F420 glutamyl tail length spectra in various habitats like manure, compost, soil, and digester sludge samples and their respective microbial communities were investigated using high performance liquid chromatography and an amplicon sequencing approach A previous in-silico study was used to identify F420 producing microorganisms. The highest concentration of cofactor F420 could be achieved in the horse manure, digester sludge, and mixed manure samples, which was approximately 100-fold higher than in all the other samples. The high content of the cofactor in the samples with high O2 availability pointed to the important role of the cofactor not only in redox reactions of anaerobic but also for aerobic microorganisms and indicated its ubiquitous character. The most abundant derivate was F420-3 comprising the largest part of the cofactor derivates in seven out of ten samples. The high abundance of F420-3 in samples with distinct properties (e.g. O2 and H2O availability) showed its important role in redox reactions of the primary and secondary metabolism among prokaryotes.

Identification of Novel Compounds Targeting the Liver X Receptor (LXR): In-silico Studies, Screening, Molecular Docking, and Chemico-pharmacokinetic Analysis

Studies have demonstrated the association between LXR activity dysregulation with many diseases, including atherosclerosis, diabetes and cancer. In recent years, several LXR agonists have surfaced, but none have been approved for human use due to adverse effects or unforeseen reasons. In this study, we first analysed the mRNA and protein expression of LXRs across tissues, network and pathway analysis, and reinterpreted their physiological function and disease association by utilizing multiple biological data repositories, including RNA-seq human protein atlas, DisGeNET, etc. Then, we performed ligand-based virtual screening, chemico-pharmacokinetic analysis, docking and simulation to identify potential new compounds. Our findings of mRNA, protein expression, network and disease enrichment analysis reveal diverse physiological functions of LXRs addressing the possibility of pharmacological manipulation with small molecules would provide therapeutic strategies for disease management. Evaluation of the docking and chemico-pharmacokinetic properties directed to the selection of LXR-623 and AZ876 as promising candidates for LXR-α and LXR-β for further in-silico investigation. Comprehensive screening for new ligands targeting LXRs based on the chemical structures of LXR-623 and AZ876, identified ZINC000005399501 and ZINC000021912941 with the highest binding affinity (−9.8 and −10.7 kcal/mol) for LXRα and LXRβ, respectively. Our results also supported in simulation study, along with favorable chemico-pharmacokinetic features.

Etodolac utility in osteoarthritis: drug delivery challenges, topical nanotherapeutic strategies and potential synergies.

Osteoarthritis (OSA) is a prevalent joint disorder characterized by losing articular cartilage, primarily affecting the hip, knee and spine joints. The impact of OSA offers a major challenge to health systems globally. Therapeutic approaches encompass surgical interventions, non-pharmacological therapies (exercise, rehabilitation, behavioral interventions) and pharmacological treatments. Inflammatory processes within OSA joints are regulated by pro-inflammatory and anti-inflammatory cytokines. Etodolac, a COX-2-selective inhibitor, is the gold standard for OSA management and uniquely does not inhibit gastric prostaglandins. This comprehensive review offers insights into OSA's pathophysiology, genetic factors and biological determinants influencing disease progression. Emphasis is placed on the pivotal role of etodolac in OSA management, supported by both preclinical and clinical evidences in topical drug delivery. Notably, in-silico docking studies suggested potential synergies between etodolac and baicalein, considering ADAMTS-4, COX-2, MMP-3 and MMP-13 as essential therapeutic targets. Integration of artificial neural network (ANN) techniques with nanotechnology approaches emerges as a promising strategy for optimizing and personalizing topical etodolac delivery. Furthermore, the synergistic potential of etodolac and baicalein warrants in-depth exploration. Hence, by embracing cutting-edge technologies like ANN and nanomedicine, the optimization of topical etodolac delivery could guide a new era of OSA treatment.

Sulfaquinoxaline-derived Schiff bases: Synthesis, characterization, biological profiling, and computational modeling

Here, six sulfaquinoxaline Schiff bases were synthesized, and various analytical techniques such as FTIR, 1HNMR, and 13CNMR were employed for the characterization. Additionally, in-vitro biological studies were performed, including antibacterial, antifungal, antioxidant, antidiabetic, and anti-inflammatory activities. Computational tools such as molecular docking, DFT, and MD simulations were applied to explore the binding interactions, molecular structure, and chemical reactivity of sulfaquinoxaline SBs. Lastly, in-silico ADMET studies were performed to investigate drug-likeness properties, toxicity, and metabolism of the synthesized SBs. The prepared SBs demonstrated strong antibacterial activity against S. agalactiae and E. coli better than the standard drug, sulfaquinoxaline. The SBs possessed non-significant antioxidant (DPPH assay) and antidiabetic activities (α-amylase and α-glucosidase). All the derivatives depicted moderate anti-inflammatory activity except 6e (IC50 131.95 µg/mL) which presented comparable activity to the standard drug, diclofenac sodium (IC50 127.27 µg/mL). Computational analyses supported the experimental results, especially for compounds 5e and 6e confirming the robust binding affinities and enduring interactions of SBs with the protein target. In-silico drug-likeness analysis and ADMET prediction demonstrated that SBs were drug-like and had a satisfactory ADMET profile.

Design and In-silico Study of ¹³¹Iodium Radiolabeled of Thiourea derivatives for Breast Cancer Treatment

Breast cancer is a serious challenge in both developed and developing countries, with current therapies still limited and potentially producing adverse side effects. To optimize breast cancer drug development, this study adopted an in-silico design approach. The aim is to develop radiopharmaceutical drugs with minimal side effects. Methods involved molecular docking analysis, molecular dynamics, drug scan, and pharmacokinetic profile prediction of the original ligan as well as the radioligand. Results showed that the radioligand had better binding energy and inhibition constant than tamoxifen as a comparator drug which is -11.31 kcal/mol and 0.00511 µM. Molecular dynamics analysis revealed that the radioligand compound exhibits comparable RMSD, RMSF, and stability metrics to the native ligand at the GRPR receptor with average RMSD and RMSF of 5.263 Å and 2.285 Å, respectively. By considering the results of these various methods, the radioligand compound shows potential as an effective radiopharmaceutical drug in breast cancer therapy.

The Oncogenic Potential of IQ Motif-Containing GTPase-Activating Protein3 in Human Bladder Cancer: An In-Silico Analysis

Introduction: IQ motif-containing GTPase-activating protein3 (IQGAP3) contributes to the progression of bladder urothelial carcinoma (BLCA), but its mechanisms are not systematically specified. Due to the oncogenic potential of IQGAP3, the current in-silico study intended to elucidate IQGAP3's role in BLCA progression. Materials and Methods: Many bioinformatics tools, including UALCAN, Kaplan–Meier plotter, TNMplot, cBioPortal, GeneMania, Enrichr, TIMER2, muTarget, and UCSC Xena, were applied in the current study. Results: The IQGAP3 level was more pronouncedly raised in BLCA tissues than in normal bladder tissues, and its increased expression was related to the advanced stage and higher grade. Enhanced IQGAP3 expression could result from its genetic alteration. Moreover, the mutation in P53 and RB1 genes was robustly associated with increased IQGAP3 expression. Besides, IQGAP3 correlative genes were dominantly involved in the cell cycle. On the other hand, IQGAP3 upregulation influenced immune checkpoint levels in the tumor microenvironment. Conclusion: The in-silico findings suggested that IQGAP3 overexpression could be a crucial biomarker in BLCA.

Synthesis and In-silico study of 5-oxo-1, 2-diphenyl-4-(phenylamino)-2,5-dihydro-1H-pyrrole-3-carboxylate

Synthesis and In-silico study of 5-oxo-1, 2-diphenyl-4-(phenylamino)-2,5-dihydro-1H-pyrrole-3-carboxylate

In-Silico exploration: Unraveling the anti-cancer potential of 8-Nitroquinoline hydrazides

The proliferation of cancer has propelled the scientific community to expedite drug discovery to nullify the threats of cancers on health segment. Addressing the adverse impact of cancer on health necessitates the effective solution. The profound activity of quinoline core appended heterocyclic derivatives against cancer proliferation impacts their significance in cancer pathology. The hydrazides of 8-nitroquinoline derivatives were synthesised, and their structures were characterized through IR, NMR and single crystal XRD techniques. Initially, the theoretical calculations like green chemistry metrics and DFT studies of the 6a-c have successfully elucidated through FMO, molecular reactivity descriptors, MEP mapping approaches. Outcomes of the studies clearly indicate that the synthesised quinoline hydrazides were highly capable to interact with the biological target entities. In-Silico studies explicit the role of organic small molecules and its efficiency to be the potent drug candidates in therapeutics. Computationally the ADMET studies and the molecular docking performance of 6a-c demonstrated to expose the pharmacokinetic behaviour and binding probability assessments with 11 different oncogenic receptors. The compound 6c could be found as favourable drug molecule adhered from its drug likeness, which comply with most of the ADMET properties. Moreover notably, methyl substituted 6c exhibits its potential binding efficiency with CDK2 and PI3K macromolecules bearing -8.7 & -7.5 kcal/mol binding affinity over 6a & 6b among the selected oncogenic proteins. The insights of in-silico studies could be validated further through in-vitro and in-vivo wet lab research works.