Screening Of Phytoconstituents Research Articles

Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease.

Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation. Additionally, elevated oxidative stress during AD stimulates the ERK1 pathway, leading to neuronal loss. Because ERK1 signaling plays a significant role in tau phosphorylation, targeting ERK1 may be therapeutically beneficial by either preventing excessive activation of the signaling pathway or altering its pathway to enhance neuroprotective effects during AD. This study employed structure-based virtual screening of phytoconstituents from the IMPPAT library. Subsequently, in-depth docking and molecular dynamics (MD) simulation studies were implemented to identify potential ERK1 inhibitors with desirable pharmacological properties. Silandrin and Hydroxytuberosone were found to be potential ERK1 inhibitors with higher affinity and specificity than the control molecule Tizaterkib. These compounds specifically bind to the ERK1 substrate binding pocket and interact with crucial residues. Finally, the elucidated compounds with ERK1 were evaluated using an all-atom molecular MD simulation to analyze structural dynamics, structural compactness, hydrogen bond dynamics, principal component analysis, and free energy landscape. The study suggested that Silandrin and Hydroxytuberosone can further be exploited as potential lead molecules for therapeutic development against ERK1-mediated AD.

In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ −8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski’s rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65. Communicated by Ramaswamy H. Sarma

Screening of phytoconstituents from Bacopa monnieri (L.) Pennell and Mucuna pruriens (L.) DC. to identify potential inhibitors against Cerebroside sulfotransferase.

Cerebroside sulfotransferase (CST) is considered a target protein in developing substrate reduction therapy for metachromatic leukodystrophy. This study employed a multistep virtual screening approach for getting a specific and potent inhibitor against CST from 35 phytoconstituents of Bacopa monnieri (L.) Pennell and 31 phytoconstituents of Mucuna pruriens (L.) DC. from the IMPPAT 2.0 database. Using a binding score cutoff of -8.0 kcal/mol with ADME and toxicity screening, four phytoconstituents IMPHY009537 (Stigmastenol), IMPHY004141 (alpha-Amyrenyl acetate), IMPHY014836 (beta-Sitosterol), and IMPHY001534 (jujubogenin) were considered for in-depth analysis. In the binding pocket of CST, the major amino acid residues that decide the orientation and interaction of compounds are Lys85, His84, His141, Phe170, Tyr176, and Phe177. The molecular dynamics simulation with a 100ns time span further validated the stability and rigidity of the docked complexes of the four hits by exploring the structural deviation and compactness, hydrogen bond interaction, solvent accessible surface area, principal component analysis, and free energy landscape analysis. Stigmastenol from Bacopa monnieri with no potential cross targets was found to be the most potent and selective CST inhibitor followed by alpha-Amyrenyl acetate from Mucuna pruriens as the second-best performing inhibitor against CST. Our computational drug screening approach may contribute to the development of oral drugs against metachromatic leukodystrophy.

Screening of Phytoconstituents in Medicinal Plants and Study of Their Effect in Seed Germination

Due to the existence of bioactive phytochemicals in plants, they have been traditionally utilized as medicine for a very long time. The present study was aimed to determine the phytoconstituents present in ten different plants collected from Katunje-Bhaktapur, Nepal. The methanol extract of the sample was used for analyzing the phytoconstituents present in the plant sample. The result revealed the existence of several phytoconstituents like alkaloid terpenoid, quinine, tannin, saponin and flavonoid in these plants. Similarly, the impact of phytoconstituents on germination of Pisum sativum seeds in water, aqueous extract, methanol, and methanol extract were analyzed. Shoot germination was retarded on all extracts.

Antioxidant, anticancer activity and phytochemical constituents of Dryopteris hirtipes (blumze) kuntze Linn.

This study was to identify the prominent bioactive components and their biological activity from hexane and ethyl acetate extracts of D.hirtipes by performing spectral studies. Leaves of D.hirtipes were extracted by solvents via Soxhlet apparatus. After extraction, column fractions were collected from two extracts of D.hirtipes and clear bands of TLC spots were identified. The screening of phytoconstituents and its functional groups from the D.hirtipes was carried out by using LC-MS ,FT-IR spectral analyses and for biological studies like antioxidant (DPPH) and anticancerous effect (HeLa and A549 cell line) of D.hirtipes. Pure spots were found in TLC in hexane and ethyl acetate extracts, responsible for polyphenolic compounds. In FTIR, extracts were analyzed and confirm the presence of functional molecules like hydroxyl and carboxylic groups, alcohols, phenols, alkanes and amine groups. Depending on the mass chromatogram (m/z) peak ratio in LC-MS, the acylphluroglucinol derivatives like Kaempferol 3-0-(4”0-acetylrutinoside), Quercetin3-0-rhamnoside, flavaspidic acid AB compounds were identified. Free radical scavenging activity was found effective in ethyl acetate than hexane. In MTT assay, cancerous activity was identified between the two extracts using cell lines like HeLa and Lung (A549) cell line. Ethyl acetate showed prominent anticancer activity.

Potential drug candidates against Hepatitis C virus: In silico screening of phytoconstituents from Phyllanthus fraternus G.L. Webster

Potential drug candidates against Hepatitis C virus: In silico screening of phytoconstituents from Phyllanthus fraternus G.L. Webster

In-silico evaluation of Bismurrayaquinone-A phytochemical as a potential multifunctional inhibitor targeting dihydrofolate reductase: implications for anticancer and antibacterial drug development

Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy −13.5 to −11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy −10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 (Bismurrayaquinone-A), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies. Communicated by Ramaswamy H. Sarma

Circulating microRNAs as novel biomarkers for measuring the potency of ginger extract against cyclophosphamide toxicity in rat renal tissues: molecular and histopathological study.

This study aims to explore underlying molecular variations in the expression of miRNAs in kidney tissues of ginger-treated and non-treated cyclophosphamide (CP)-intoxicated rats. A total of 40 adult male Wistar rats were randomly divided into four groups of 10 each: Group I (control: received normal food and water), Group II (received ginger at a dose of 300 mg/kg), Group III (received CP 75 mg/kg, i.p.), and Group IV (received the same dose of CP and ginger extract). Rats received a single injection of 75 mg/kg CP on days 3, 4, 5, 19, 20, and 21. In CP-intoxicated rats, the treatment with ginger extract at a dose of 300 mg/kg was received by oral gavage starting seven days before CP and continuing throughout the duration of the experiment for four weeks. Molecular variations in the expression of miRNAs, apoptotic genes, histological kidney damage, and abnormal kidney function in control, ginger, and CP-intoxicated rats were identified by using real-time RT-PCR Analysis, immunohistochemical, and colorimetric assays. In addition, HPLC analysis and liquid chromatography spectrophotometry analysis using Diphenyl-1-picrylhydrazyl (DPPH) radical, and Β-Carotene-linoleic acid reagents were applied respectively for in-vitro screening of phytoconstituents and antioxidant activity for ginger extract. The kidney tissues of CP-intoxicated rats displayed an increase in lipid peroxidation marker malonaldehyde (MDA), DNA damage, and fibrosis markers like hyaluronic acid (HA) and hydroxyproline Hypx) with a decrease in the superoxide dismutase (SOD) and total antioxidant capacity (TAC). In addition, molecular expressions of mRNA fibrotic genes such as collagen, type 1, alpha 1 (COL1A1), and α-smooth muscle actin (αSMA). Molecular expressions of levels of B-cell lymphoma 2 (BCl-2) mRNA gene were down-regulated, and the expression of mRNA apoptotic; BCL2 associated X gene (Bax), caspase-3, Bax/BCl-2 ratio genes were significantly up-regulated respectively. Moreover, cellular oxidative genes, erythroid 2-related factor (Nrf2), and heme oxygenase-1 (HO-1) were down-regulated, respectively. The miR-155-5p, miR-34a-5p, miR-21-5p significantly increased while the miR-193b-3p, miR-455-3p, and miR-342-3p significantly decreased. Ginger also increased the expression of Nrf2, HO-1, and BCl-2 genes in the kidneys of rats induced with CP. In addition, active phytoconstituents, particularly 6]]-shogaol and 6]]-gingerol, were significantly identified in ginger extract using HPLC analysis. Antioxidant activity of these active metabolites were shown to be higher against in vitro free radicals (DPPH and Β-Carotene-linoleic acid), suggesting the potential antioxidant and antiapoptotic properties of ginger against CP-toxicity. Treatment with ginger in rats induced with CP resulted in significant improvement in the expression of certain molecular miRNAs. The kidney tissues of these rats showed a marked decrease in the expression of miR-155-5p, miR-34a-5p, and miR-21-5p, while the levels of miR-193b-3p, miR-455-3p, and miR-342-3p were observed to increase significantly. In conclusion, ginger can protect rats from CP-induced nephrotoxicity.

A REVIEW ON PHYTOCONSTITUENTS AND PHARMACOLOGICAL PROPERTIES OF SANSEVIERIA TRIFASCIATA (Snake Plant)

Sansevieria trifasciata belongs to Agavaceae family which is frequently found in Indonesia. It is found in tropical and subtropical regions, stretching from Africa to Southeast Asia and the islands of the Indian Ocean. It is an evergreen, succulent, perennial plant that grows long, narrow, sword-shaped leaves up to 75 cm long that can be upright or slightly spreading from a rhizomatous base. The review was based on the screening of phytoconstituents and pharmacological activities of Sansevieria trifasciata plant. It has various chemical constiutents i.e., palmitic Acid, methyl linoleate, methyl linolenate, phytol, linoleic acid, oleic acid, stearic acid, stigmasterol etc. According to research, Sansevieria trifasciata leaf is frequently used to treat bronchitis, asthma, food poisoning, toxaemia coughs, snake bites and insect bites. The LD50 value was found to be 774.60 mg/kg, and oral dosage of 18,000 mg/kg did not result in animal mortality or any unfavourable behavioural effects. It concludes that S. trifasciata is the rich source of numerous chemical constituents having multiples of traditional uses. It has been confirmed in previous studies for diverse pharmacological activities including anti-ulcer, antibacterial, antioxidant, antidiabetic, antibacterial, anthelmintic, analgesic, anti-inflammatory, cytotoxic, anticancer, and effective in alopecia.

Analysis of Biochemical and Antimicrobial Properties of Bioactive Molecules of Argemone mexicana.

This study identified phytochemicals in Argemone mexicana (A. mexicana) extracts that are responsible for its medicinal properties, and the best solvent for their extraction. The extracts of the stem, leaves, flowers, and fruits of A. mexicana were prepared at low (corresponding to room temperature) and high temperatures (corresponding to the boiling points) in various solvents, viz., hexane, ethyl acetate, methanol, and H2O. The UV-visible absorption spectra of various phytoconstituents in the isolated extracts were determined through spectrophotometry. Qualitative tests for the screening of phytoconstituents in the extracts were performed to identify various phytochemicals. We identified the presence of terpenoids, alkaloids, cardiac glycosides, and carbohydrates in the plant extracts. The antioxidant and anti-human immunodeficiency virus type 1 reverse transcriptase (anti-HIV-1RT) potential, as well as the antibacterial activity of various A. mexicana extracts were determined. These extracts showed strong antioxidant activities. The extracts exhibited antimicrobial activities against Salmonella typhi, Staphylococcus epidermis, Citrobacter, Neisseria gonorrhoeae, and Shigella flexineri. These extracts significantly inhibited HIV-1 reverse transcriptase activity. The aqueous leaf extract prepared at a temperature equivalent to the boiling point, i.e., 100 °C, was identified to be the most active against pathogenic bacteria and HIV-1 RT.

Pharmacoinformatics approach for the screening of Kovidra (Bauhinia variegata) phytoconstituents against tumor suppressor protein in triple negative breast cancer

Globally, 2.3 million women were diagnosed with breast cancer, with 6,85000 mortalities in year 2021; making it the world’s most prevalent cancer. This growing global burden necessitates a new treatment option, and plant-based medicines offers a promising alternative to conventional cancer treatment. In this work, screening of phytoconstituents of an indigenous therapeutic plant, Bauhinia variegata carried out for potential regulator of tumor suppressor protein p53. Here, an in-silico analysis was employed to develop more effective, pharmaceutically potent small drug-like compounds that target tumor suppressor protein p53. The methanol and aqueous powdered extracts of Bauhinia variegata were prepared and phytochemically evaluated along with antioxidant property evaluation. The LC50 of methanol (325.33 µg/ml) and aqueous extract (361.15 µg/ml) showed their cytotoxic characteristics. Further, GCMS analysis of both the extracts reveals total 57 secondary metabolites. Among these, four lead compounds; compound 1, compound 2, compound 3 and compound 4 were found to have the highest binding ability (-8.15 to −5.40 kcal/mol) with p53. MD simulation and binding free energy validates these findings with highest binding free energy (-67.09 ± 4.87 kcal/mol) towards p53 by the lead phytocompound 2. Selected compounds exhibit excellent pharmacokinetic features and drug-like characteristics. The acute toxicity (LD50) values of the lead phytocompounds ranges from 670 mg/kg to 3100 mg/kg, with toxicity classes of IV and V. As a result, these druggable phytochemicals could serve as potential lead applicants for triple negative breast cancer treatment. However, more in vitro and in vivo research is planned to produce future breast cancer medicine. HIGHLIGHTS Screening of phytoconstituents of an indigenous therapeutic plant, Bauhinia variegata, for potential regulator of tumor suppressor protein p53. The LC50 of methanol (325.33µg/ml) and aqueous extract (361.15µg/ml) showed their cytotoxic characteristics. GCMS analysis of both the extracts reveals total 57 secondary metabolites. Among these, four lead compounds were found to have the highest binding affinity (-8.153 to -5.401 kcal/mol) with tumor suppressor protein p53. MD simulation along with the Prime MM/GBSA binding free energy validates this discovery with highest binding free energy (-67.09 ± 4.87 kcal/mol) towards p53 by the lead compound 2. The acute toxicity (LD50) values of the lead phytocompounds ranges from 670 mg/kg to 3100 mg/kg, with toxicity classes of IV and V. As a result, these druggable phytochemicals could serve as potential lead applicants for triple negative breast cancer treatment. Communicated by Ramaswamy H. Sarma

Percolation and Soxhlet Extraction Methods Use for Screening of Phytoconstituents in Sundried Leaves of Moringa oleifera

Percolation and Soxhlet Extraction Methods Use for Screening of Phytoconstituents in Sundried Leaves of Moringa oleifera

Qualitative screening and Quantitative determination of secondary metabolites from different plant extracts of Solanum khasianum Clarke

The medicinal plants have gained significant importance in traditional medicine and pharmacy due to wide variety of curative properties. The medicinal properties of the plants rely on the presence of various phytoconstituents. The present study focused on screening of phytochemicals from different parts (leaf, stem, petiole, fruit and root) of Solanum khasianum using solvents with varying polarity like methanol, butanol, chloroform, acetonitrile and water. The qualitative screening of phytoconstituents showed the existence of alkaloids, flavonoids, phenols, tannins, steroids, saponins and absence of quinones in all 25 extracts tested. The quantitative determination showed that root extract contains considerable amounts of total flavonoids (214.74±0.45), total phenols (183.47±0.38), total alkaloids (132.46±0.28), total antioxidants (95.66±0.27), total tannins (14.66±0.07) whereas total saponins were present in high content in fruit methanolic extract (44.99±0.33). The presence of these phytoconstituents indicates the therapeutic potential of S. khasianum and scientifically validates the traditional use of this plant.

Screening of Phytoconstituents from Traditional Plants against SARSCoV- 2 using Molecular Docking Approach

Background: The emergence of COVID-19 as a fatal viral disease encourages researchers to develop effective and efficient therapeutic agents. The intervention of in silico studies has led to revolutionary changes in the conventional method of testing the bioactivity of plant constituents. Objective: The current study deals with the investigation of some traditional immunomodulators of plant origin to combat this ailment. Materials and Methods: A total of 151 phytomolecules of 12 immunomodulatory plants were evaluated for their inhibitory action against the main protease (PDB ID: 7D1M) and NSP15 endoribonuclease (PDB ID: 6WLC) by structure-based virtual screening. In addition, the promising molecules with ligand efficiency of more than -0.3(kcal/mol)/heavy atoms were further predicted for pharmacokinetic properties and druggability using the SwissADME web server, and their toxicity was also evaluated using Protox-II. Result: Myricetin-3-O-arabinofuranoside of cranberry plant was found to be the most potential candidate against both enzymes: main protease (–14.2 kcal/mol) and NSP15 endoribonuclease (–12.2 kcal/mol). Conclusion: The promising outcomes of the current study may be implemented in future drug development against coronavirus. The findings also help in the development of lead candidates of plant origin with a better ADMET profile in the future.

Comparative inhibitory screening of phytoconstituents from Capparis decidua against various ailments targets: a novel In-silico semblance ADME/Tox profiling studies

Comparative inhibitory screening of phytoconstituents from Capparis decidua against various ailments targets: a novel In-silico semblance ADME/Tox profiling studies

Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches.

Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of Ocimum tenuiflorum phytocompounds against DPP4. In this regard, three phytocompounds (1S-α-pinene, β-pinene, and dehydro-p-cymene) from O. tenuiflorum have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-p-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future.

Screening of phytoconstituents and antibacterial effects of leaf & stem of Ailanthus excelsa against E. Coli, S. Aureus, A. Niger & A. Flavus

The research was aimed as screening of phytoconstituents and antibacterial effects of Leaf & Stem of Ailanthus excelsa against E. Coli, S. Aureus, A. Niger & A. Flavus. The plants were collected from Bareilly region, Uttar Pradesh and authentication was done by CIMAP, Lucknow. The collected plant material was dried in shade and ground in the grounder. The dried powdered drug material was extracted by 9 different solvents by cold maceration for 12 hrs at room temperature. Mayer’s, Hager’s tests, Fehling’s Wager’s and Molisch test were used for detection of alkaloids, glycosides, saponins, terpenoids etc. After the extraction was complete, it was tested against various species such as E. coli, S. aureus, S. niger and A. Flavus for its antimicrobial potential. The results indicate that methanolic extract showed highest level of phytoconstituents such as alkaloids, glucosides, saponins, terpenoids, flavonoids, and carbohydrates. Extract showed significant antibacterial potential against all the species tested with. In conclusion, this research suggests, that novel molecules should be identified and isolated responsible for specific pharmacological activity.

Qualitative and quantitative screening of phytoconstituents and characterization of various extracts of Wedelia trilobata leaf extracts

The birth control pills (contraceptive) are safe, in some cases the combination of the contraceptive pill can increase your risk of health. The side effects include heart attack, stroke, blood clots, and liver tumors. In very rare cases, they can lead to death. The risk of health problems and side effects were minimal or no side effects recorded while using the herbal contraceptives. The present investigation was focused on the preliminary phytochemical analysis, UV-VIS spectrum and Fourier Transform Infrared Spectral analysis and HPLC analysis of Wedelia trilobata L. The leaves were extracted using soxhlet extractor with seven different solvent in the order of relative polarity (aqueous, methanol, ethanol, acetone, petroleum ether, benzene and hexane) the leaves of the plant of Wedelia trilobata L. were tested for the availability of alkaloids, glycosides, flavonoids, phenols, saponins, steroids, amino acids, tannins, terpenoids, quinones, anthraquinones etc. And the phenol, flavonoid and terpenoids were analysed quantitatively. The UV-VIS spectrum showed the peaks with the absorption for the seven solvents respectively. The FT-IR spectrum showed the presence of alcohols, phenols, alkanes, alkynes, alkyl halides, aldehydes, aromatics, nitro compounds and amines. With the HPLC results we confirm that the compound caryophyllene which was used as contraceptive now a days was present in the two extracts (aqueous and ethanol) The results confirm the fact that this plant possesses important bioactive constituents useful for our health, so further scientific investigation is needed to investigate the biological activities of this plant.

Bioactive Phytoconstituents as Potent Inhibitors of Tyrosine-Protein Kinase Yes (YES1): Implications in Anticancer Therapeutics.

Tyrosine-protein kinase Yes (YES1) belongs to the Tyrosine-protein kinase family and is involved in several biological activities, including cell survival, cell–cell adhesion, cell differentiation, and cytoskeleton remodeling. It is highly expressed in esophageal, lung, and bladder cancers, and thus considered as an attractive drug target for cancer therapy. In this study, we performed a virtual screening of phytoconstituents from the IMPPAT database to identify potential inhibitors of YES1. Initially, the molecules were retrieved on their physicochemical properties following the Lipinski rule of five. Then binding affinities calculation, PAINS filter, ADMET, and PASS analyses followed by an interaction analysis to select safe and clinically better hits. Finally, two compounds, Glabrene and Lupinisoflavone C (LIC), with appreciable affinities and a specific interaction towards the AlphaFold predicted structure of YES1, were identified. Their time-evolution analyses were carried out using an all-atom molecular dynamics (MD) simulation, principal component analysis, and free energy landscapes. Altogether, we propose that Glabrene and LIC can be further explored in clinical settings to develop anticancer therapeutics targeting YES1 kinase.

In-silico Screening of Phytoconstituents on Wound Healing Targets - Approaches and Current Status.

Over recent years, there has been tremendous research focused on the effective utilization of natural products in wound management. Natural or herbal products contain several phytoconstituents that may act on various stages in wound healing and thereby provide a multi-targeted approach especially in the treatment of chronic wounds. Currently, attempts have been made to screen the phytoconstituents present in herbs on various targets involved in wound healing. This review includes a systematic evaluation of scientific reports by various groups of researchers on the herbals evaluated for wound management, their phytochemical profiling, pre-clinical studies, and molecular modeling studies. Various wound targets discussed include Interleukin-1, Interleukin-6, Tumor necrosis factor-α (TNF-α), Thymosin beta-4 (Tβ-4) that regulate the early inflammatory stage and the novel T cell immune response cDNA 7(TIRC7) that regulates angiogenesis. Also, neuropeptides P and Y act on the inflammatory, migratory, and proliferation phases, and growth factors like vascular endothelial growth factor family (VEGF) and placental growth factor family (PGF) are involved in angiogenesis, while the role of Fibroblast growth factor in tissue remodeling is discussed. As many of the natural products include polyherbal systems, this approach can help in the judicious selection of a combination of herbs that will act on multiple targets in the wound healing process and provide a multi-factorial approach in wound management.