Amino Residues Research Articles

Anticancer Potential of Cyanidin and Cyanidin-3-Glucoside Through TrkB Receptor Inhibition: Evidence From Molecular Interaction Docking

Cancer remains a global health problem with persisten demand on therapeutic development to inhibit cancer cells growth without harmful effects on healthy cells. Plant bioactive compounds are intensively studied as anticancer via several signalling pathway. Anticancer therapy via inhibition of tropomyosin kinase receptor-B (TrkB) signal was previously proposed as target therapy. The role of plant metabolites cyanidin and cyanidin-3-glucoside as TrkB inhibitor is has not been investigated. This study was aimed to identify physicochemical of cyanidin and cyanidin- 3-glucoside as well as determine it’s role towards TrkB receptor signalling pathway through in silico approach. Molecular docking was performed using Hex 8.0.0 software and visualizes using Discovery Studio Visualizer. The energy binding of TrkB with cyanidin and cyanidin-3-glucoside was -263,21 kcal/mol and 281,65 kcal/mol respectively. Complex of cyanidin-3-glucoside had hydrogen and hydrophobic bond more than TrkB-cyanidin complex. The hydrogen bond formed at Lys637, Arg558 and Gly 561 amino residues. Physicochemical analysis demonstrated that both ligand are potential as kinase enzyme inhibitor. Cyanidin-3-glucoside was predicted more potential as anticancer than cyanidin via TrkB receptor inhibition. Future studies are required to confirm current finding both in-vitro and in-vivo models.

A derivative of tanshinone IIA and salviadione, 15a, inhibits inflammation and alleviates DSS-induced colitis in mice by direct binding and inhibition of RIPK2.

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions primarily affecting the gastrointestinal tract. Previous studies established the role of the NF-κB signaling pathway in the development of IBDs, suggesting that anti-inflammatory therapies might offer a viable treatment strategy. Tanshinone IIA and salviadione, both derived from Salviae Miltiorrhizae Radix et Rhizoma, possess anti-inflammatory and anti-oxidative activities. A series of new compounds were synthesized by hybridizing salviadione with tanshinone. Among these compounds, 15a showed beneficial effects in LPS-induced acute lung injury and diabetes-induced renal injury mouse models. The current study explored the therapeutic efficacy of 15a using both acute and chronic colitis models and elucidated the underlying mechanisms. DSS-induced colitis models were established in mice, where acute colitis was treated with compound 15a (5 or 10 mg·kg-1·d-1) for 8 days, while chronic colitis mice received compound 15a (5 or 10 mg·kg-1·d-1, i.g.) during 2.5% DSS administration. The 15a treatment significantly alleviated DSS-induced pathological and inflammatory damages in both acute and chronic colitis mouse models. In mouse intestinal epithelial cell line MODE-K, pretreatment with compound 15a (5 or 10 μM) significantly suppressed LPS + L18-MDP-induced inflammatory responses. The receptor-interacting serine/threonine kinase 2 (RIPK2) was identified as a direct binding target of compound 15a using microarrays and recombinant human proteins. Moreover, 15a could directly bind to and inhibit the phosphorylation of RIPK2, leading to the suppression of the NF-κB and MAPK signaling pathways. Furthermore, LEU153 and VAL32 were identified within the KD domain of RIPK2 as critical amino residues for the binding of 15a. Briefly, the current findings demonstrate that compound 15a holds promise as a therapeutic agent for managing acute and chronic colitis.

Chemical Capture and Sensing of Bovine Serum Albumin with Phenothiazinylcarbaldehyde-Labeled 2′-Deoxyuridine

AbstractChemical-capture-mediated sensing has had a great impact on proteomic research. Toward this end, we demonstrate the chemical trapping of BSA by the reactive formyl functionality of a newly developed fluorescent nucleoside probe, formylphenothiazine-labeled-2′-deoxyuridine. The probe is capable of trapping BSA via Schiff base formation leading to fluorescence ‘switch-on’ sensing with a large hypsochromic shift of ca. 100 nm. The α-amylase does not show any significant change in fluorescence response, demonstrating the efficiency of the probe in selective sensing of BSA. Docking studies suggest the preferential interaction of the phenothiazinylcarbaldehyde-labeled dU with the residual amino acids in site I of the BSA protein as compared to site II.

Comprehensive Cell Biological Investigation of Cytochalasin B Derivatives with Distinct Activities on the Actin Network.

In search of a more comprehensive structure-activity relationship (SAR) regarding the inhibitory effect of cytochalasin B (2) on actin polymerization, a virtual docking of 2 onto monomeric actin was conducted. This led to the identification of potentially important functional groups of 2 (i.e., the NH group of the isoindolone core (N-2) and the hydroxy groups at C-7 and C-20) involved in interactions with the residual amino acids of the binding pocket of actin. Chemical modifications of 2 at positions C-7, N-2, and C-20 led to derivatives 3-6, which were analyzed for their bioactivities. Compounds 3-5 exhibited reduced or no cytotoxicity in murine L929 fibroblasts compared to that of 2. Moreover, short- and long-term treatments of human osteosarcoma cells (U-2OS) with 3-6 affected the actin network to a variable extent, partially accompanied by the induction of multinucleation. Derivatives displaying acetylation at C-20 and N-2 were subjected to slow intracellular conversion to highly cytotoxic 2. Together, this study highlights the importance of the hydroxy group at C-7 and the NH function at N-2 for the potency of 2 on the inhibition of actin polymerization.

Molecular Interactions Governing the Rat Aryl Hydrocarbon Receptor Activities of Polycyclic Aromatic Compounds and Predictive Model Development.

Polycyclic aromatic compounds (PACs) exhibit rat aryl hydrocarbon receptor (rAhR) activities, leading to diverse biological or toxic effects. In this study, the key amino residues and molecular interactions that govern the rAhR activity of PACs were investigated using in silico strategies. The homology model of rAhR was first docked with 90 PACs to yield complexes, and the results of the molecular dynamics simulations of 16 typical complexes showed that the binding energies of the complexes range from -7.37 to -26.39 kcal/mol. The major contribution to the molecular interaction comes from van der Waals forces, and Pro295 and Arg316 become the key residues involved in most complexes. Two QSAR models were further developed to predict the rAhR activity of PACs (in terms of log IEQ for PACs without halogen substitutions and log%-TCDD-max for halogenated PACs). Both models have good predictive ability, robustness, and extrapolation ability. Molecular polarizability, electronegativity, size, and nucleophilicity are identified as the important factors affecting the rAhR activity of PACs. The developed models could be employed to predict the rAhR activity of other reactive PACs. This work provides insight into the mechanisms and interactions of the rAhR activity of PACs and assists in the assessment of their fate and risk in organisms.

Virtual design and screening of new (+)-catechin derivates N- and/or S-heterocyclic fragment for anti-malarial and anti-SARS-CoV-2 activities by In silico simulation

Hemisynthesis makes it possible to improve the activity or reduce the toxicity of a biocompound by modifying or adding peripheral groups. Catechin present in different plant species was known for its moderate anti-malarial and anti-SARS-CoV-2 activities. The aim of this work was focused on the identification of new compounds with potential anti-SARS-CoV-2 and/or anti-malarial activities, evaluated through In silico simulation. A polyphenol pharmacophore model, based on (+)-catechin (1) was virtually constructed using previously reported inhibitors. N- and/or S-heterocyclic fragments were inserted on the backbone of (+)-catechin and 12 pharmacophore hypotheses were studied. This study targeted 3 proteins biologically responsible for SARS-CoV-2 (PDB ID: 7JYC, 6M0J, and 6HZD) and one protein responsible for malaria (PDB ID: 3SRJ). Molecular docking had shown that the new catechin-aldehyde candidates have good Ligand-Protein affinity in terms of free energy compared to the study reference Narlaprevir and Artesunate for SARS-CoV-2 and malaria respectively. Theoretically, most compounds didn’t show toxicity except compounds 2a, 2i, and 2k, exhibiting hepatotoxic activity. Molecular dynamics was used to prove and assess their binding stability to the target protein for each activity. The 3SRJ-2f and 6HZD-2l structures were selected for anti-malarial and anti-SARS-CoV-2 activity respectively. The 3SRJ-2f and 6HZD-2l complexes showed stable interactions to 100 ns between the inhibitor fragments and the residual amino acids of the protein. To conclude, these novel compounds are probably to become promising lead molecules for the development of effective anti-SARS-CoV-2 and/or anti-malarial of all drugs. Keywords: Catechin, Anti-malarial, Anti-SARS-CoV-2, Docking and Dynamic Molecular, ADMET Analysis.

An all-in-one smartphone-assisted ratiometric fluorescent device for visual and quantitative detection of glutathione

The daily consumption of foods abundant in Glutathione (GSH) can be supplemented to maintain the homeostasis of GSH in human health and alleviate pathologies resulting from abnormal GSH levels. The fluorescence-based visual determination of GSH has gradually attracted the attention of researchers due to its robust performance and versatile implementation. However, the current GSH visual strategy primarily relies on variations in fluorescence intensity at a single emission wavelength, which poses challenges for naked-eye and portable readout, as well as distorted signals caused by complex matrix effects in real samples. Herein, a ratiometric fluorescence sensor based on carbon dots (CDs) combined with an all-in-one 3D-printed smartphone-based device was successfully developed for low-cost, visual and rapid detection of GSH without the need for an external excitation light source. The ratiometric fluorescent materials were synthesized by conjugating blue carbon dots (B-CDs) with yellow carbon dots (Y-CDs) through the utilization of selected Cu2+ ions. The resulting mechanism demonstrated that the coordination interaction between Cu2+ and residual aromatic amino groups in Y-CDs (Y-CDs-Cu2+) contributed to a newly emitted peak at 580 nm, thereby inducing fluorescence resonance energy transfer from B-CDs to Y-CDs-Cu2+. A linear correlation was found between GSH concentrations and R/B values in the range of 10–100 μM, with a limit of detection observed at 4.8 μM. By utilizing this portable device in combination with RGB analysis, the quantitative detection of GSH can be achieved even in complex food matrices such as tomatoes and grapes. The universality of this all-in-one device was further validated by pre-spraying CDs onto a paper strip for visual measurement of GSH. This work offers a portable, visual, and accessible approach to evaluating food safety and nutrition, thereby demonstrating significant economic value and holding profound implications for human health.

Molecular analysis of changes in DNA binding affinity and bending extent induced by the mutations on the aromatic amino residues in Cren7.

Proteins from Crenarchaeal organisms exhibit remarkable thermal stability. The aromatic amino acids in Cren7, a Crenarchaeal protein, regulate protein stability and further modulate DNA binding and its compaction. Specific aromatic amino acids were mutated, and using spectroscopic and theoretical approaches, we have examined the structure, DNA binding affinity, and DNA bending ability of mutants. and compared with wild-type (WT) Cren7. The reverse titration profiles were analysed by a noncooperativeMcGhee-von Hippel model to estimate affinity constant (Ka) and site size (n) associated with binding to the DNA. Biolayer interferometry (BLI) measurements showed that the binding affinity decreased at higher salt concentrations. For theoretical analysis of extent of DNA bending, radius of gyration and bending angle were compared for WT and mutants. Time evolution of order parameters based on translational and rotational motion of tryptophan residue (W26) was used for qualitative detection of stacking interactions between W26 of Cren7 and DNA nucleobases. It was observed that orientation of W26 in F41A favoredformation of a new lone pair-lone pair interaction between DNA and Cren7. Consequently, in thermostable proteins, the aromatic residues at the terminus maintain structural stability, whereas the residues at the core optimize the degree of DNA bending and compaction.

New substituted benzenesulphonamoyl ‘Cys-Gly’ dipeptide carboxamide derivatives: Design, synthesis, characterization and pharmacological studies

Twelve new sulphonamide (Cys-Gly) dipeptide carboxamide derivatives 17a–17l were designed, prepared and characterized through spectroscopic techniques and their pharmacological properties investigated. The molecular docking analyses revealed good interactions of the derivatives with the desired amino residues active pockets. In vitro antimicrobial, in vivo antimalarial, haematological and other related tests (liver and kidney) were also conducted. Compounds 17b exhibited good minimum inhibitory concentration (MIC) results (0.9–11) mg/mL for the studied organisms when compared with ciprofloxacin and fluconazole. Derivatives 17a −17l showed parasitaemia inhibition in the range (31.11–67.78) % on the fourth day after treating the animals with 40 mg/kg of the compounds. Derivative 17b also displayed the highest parasitaemia inhibition (67.78 %) comparable with the standard (Lumenfantrine) 75.27 %. The prepared derivatives showed promising pharmacological properties with regards to hematological, liver and kidney function tests.

Identification of mycobacterial Thymidylate kinase inhibitors: a comprehensive pharmacophore, machine learning, molecular docking, and molecular dynamics simulation studies

Thymidylate kinase (TMK) is a pivotal enzyme in Mycobacterium tuberculosis (Mtb), crucial for phosphorylating thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), thereby playing a critical role in DNA biosynthesis. Dysregulation or inhibition of TMK activity disrupts DNA replication and cell division, making it an attractive target for anti-tuberculosis drug development. In this study, the statistically validated pharmacophore mode was developed from a set of known TMK inhibitors. Further, the robust pharmacophore was considered for screening the Enamine database. The chemical space was reduced through multiple molecular docking approaches, pharmacokinetics, and absolute binding energy estimation. Two different molecular docking algorithms favor the strong binding affinity of the proposed molecules towards TMK. Machine learning-based absolute binding energy also showed the potentiality of the proposed molecules. The binding interactions analysis exposed the strong binding affinity between the proposed molecules and active site amino residues of TMK. Several statistical parameters from all atoms MD simulation explained the stability between proposed molecules and TMK in the dynamic states. The MM-GBSA approach also found a strong binding affinity for each proposed molecule. Therefore, the proposed molecules might be crucial TMK inhibitors for managing Mtb inhibition subjected to in vitro/in vivo validations.

Effect of crosslinking density on the self-healing and self-reporting properties of epoxy anti-corrosion coatings

This work developed a novel coating with self-healing and self-reporting performance by embedding polyurethane/poly-(urea-formaldehyde) (PU/UF) microcapsules in a shape memory epoxy polymer. 2’7’-Dichlorofluorescein (DCF) and linseed oil were applied as the coloring agent and healing agent, respectively, which are encapsulated into the PU/UF microcapsules (DL@PU/UF microcapsules) via a facile one-step method. To adjust the shape memory effect and the self-reporting performance of epoxy system, two kinds of curing agents (D230 and D400) were reacted with bisphenol A diglycidyl ether epoxy monomer to design a series of coating samples, finally the optimal coating system was selected by three indexes including barrier performance, residual amino content and coating hardness. When the composite coating was damaged, DCF can flow out of the broken microcapsules and react with the residual amino groups in the epoxy coating matrix, which can be recognized red signals in natural light and yellow fluorescent signals under ultraviolet light irradiation. More importantly, the excellent self-reporting property of the coating can be achieved on various metal substrates that broaden the application range of the coating. As for self-healing performance, the damaged coating can be healed quickly due to the shape memory effect of the coating as well as the filling of linseed oil in the scratched region. The Rct value of the healed coating containing 6 % DL@PU/UF microcapsules after immersing in 3.5 wt% NaCl solution for 5 days was more than 3 times that of the scratched coating, and the Rc value was about 16 times that of the scratched coating, indicating its corrosion protection performance. The novel coting not only achieve timely self-reporting ability of color and fluorescence, but also rapidly repair the coating damage, which is essential to practical applications.

The Discovery of GIT1/β-Pix Inhibitors: Virtual Screening and Biological Evaluation of New Small-molecule Compounds with Anti-invasion Effect in Gastrointestinal Neoplasms.

GIT1 (G-protein-coupled receptor kinase interacting protein-1) has been found to be highly related with cancer cell invasion and metastasis in many cancer types. β-Pix (p21-activated kinase-interacting exchange factor) is one of the proteins that interact with GIT1. Targeting GIT1/β-Pix complex might be a potential therapeutic strategy for interfering cancer metastasis. However, at present, no well-recognized small-molecule inhibitor targeting GIT1/β-Pix is available. Thus, we aim to discover novel GIT1/β-Pix inhibitors with simple scaffold, high activity and low toxicity to develop new therapeutic strategies to restrain cancer metastasis. GIT1/β-Pix inhibitors were identified from ChemBridge by virtual screening. Briefly, the modeling of GIT1 was performed and the establishment of GIT1/β-Pix binding pocket enabled the virtual screening to identify the inhibitor. In addition, direct binding of the candidate molecules to GIT1 was detected by biolayer interferometry (BLI) to discover the hit compound. Furthermore, the inhibitory effect on invasion of stomach and colon cancer cells in vitro was carried out by the transwell assay and detection of epithelial-mesenchymal transition (EMT)-related proteins. Finally, the binding mode of hit compound to GIT1 was estimated by molecular dynamics simulation to analyze the key amino residues to guide further optimization. We selected the top 50 compounds from the ChemBridge library by virtual screening. Then, by skeleton similarity analysis nine compounds were selected for further study. Furthermore, the direct interaction of nine compounds to GIT1 was detected by BLI to obtain the best affinitive compound. Finally, 17302836 was successfully identified (KD = 84.1±2.0 μM). In vitro tests on 17302836 showed significant anti-invasion effect on gastric cancer and colorectal cancer. We discovered a new GIT1/β-Pix inhibitor (17302836) against gastrointestinal cancer invasion and metastasis. This study provides a promising candidate for developing new GIT1/β-Pix inhibitors for tumor treatment.

Inhibitory effect and the involved mechanism of furaneol on enzymatic browning of potatoes

Enzymatic browning is an important issue impacting the shelf life of fresh-cut potatoes. Using browning inhibitors is an effective method to solve the issue. This research aimed to identify novel and safe inhibitors of enzymatic browning. The research first investigated the inhibitory role of furan compounds in enzymatic browning, then explored the anti-browning effect of furaneol and the involved mechanism. Among the eight tested furan compounds classified as flavorings in food additives, seven showed anti-browning effects, of which three demonstrated superior efficacy in delaying browning compared to the others. Based on the efficacy and odor, furaneol as one natural flavor composition of fresh fruit was selected to be further investigated. At 4 °C, control potatoes browned on day 1. However, furaneol at concentrations of 4 and 8 mM prevented the fresh-cut potatoes from browning for up to 10 d, and their anti-browning efficacies reached that of sodium bisulfite. Sensory evaluation showed the treated fresh-cut potatoes exhibited a slight and acceptable sweet aroma, which quickly disappeared after heat cooking. Further research revealed furaneol reduced the activity of polyphenol oxidase (PPO), chelated Cu2+, and acted as a mixed-type inhibitor of PPO with competitive inhibition being the dominant. Circular dichroism analysis indicated furaneol decreased α-helix content, increased the β-fold content, and altered the secondary structure of PPO. Fluorescence quenching data showed furaneol can form complexes with PPO, quench the fluorescence produced by PPO and change its tertiary structure. Molecular docking suggested that furaneol could enter the active center region near copper ions and interact with surrounding amino residues through van der Waals force, pi-alkyl interactions and carbon-hydrogen bonds. Furaneol can also cause the brown pigment colorless to a certain extent. Moreover, furaneol addition also improved the antioxidant capacity of enzymatic browning reaction system. Our study first reported the inhibitory effect of furan compounds on enzymatic browning and furaneol has great potential as an anti-browning inhibitor for fresh-cut produce in future.

Kinetic nitrogen isotope effects of 18 amino acids degradation during burning processes

Understanding the nitrogen isotopic variations of individual amino acids (AAs) is essential for utilizing the nitrogen isotope values of individual amino acids (δ15N-AA) as source indicators to identify proteinaceous matter originating from biomass combustion processes. However, the nitrogen isotope effects (ε) associated with the degradation of individual amino acids during combustion processes have not been previously explored. In this study, we measured the nitrogen isotope values of residual free amino acids -following a series of controlled combustion experiments at temperatures of 160–240 °C and durations of 2 min to 8 h, as described in Part 1. δ15N values of proline, aspartate, alanine, valine, glycine, leucine, and isoleucine are more positive than their initial δ15N values after prolonged combustion. Variations in δ15N values of the most AAs conform to the Rayleigh fractionation during combustion and their nitrogen isotope effects (ε) are greatly impacted by their respective combustion degradation pathways. This is the first time the ε values associated with the degradation pathways of AAs during combustion have been characterized. Only the ε values associated with Pathway 1 (dehydration to form dipeptide) and 2 (simultaneous deamination and decarboxylation) are found to be significant and temperature-dependent, ranging from + 2.9 to 6.4‰ and + 0.9‰ to + 3.8‰, respectively. Conversely, ε values associated with other pathways are minor. This improves the current understanding on the degradation mechanisms of protein nitrogen during biomass burning.

The effect of dietary sodium octanoate on Ghrelin concentration and feed intake in chickens and turkeys: a comparative study

Active ghrelin (AG) is produced through the post-translational addition of n-octanoic acid to the amino residue Ser-3, making it the natural ligand for the ghrelin receptor. The synthesis of AG is contingent upon specific dietary fatty acids as substrates for the acylation process. Prior studies have demonstrated that AG infusion can lead to reduced feed intake (FI) in broiler chickens, suggesting that manipulating AG may serve as an alternative to quantitative feed restriction in broiler breeders. In this study, we evaluated the effect of dietary sodium octanoate (Octanoate) on FI, water intake (WI), BW, total ghrelin, and β-hydroxybutyrate (BHB) concentration in two avian species. Broiler chickens and turkeys were reared as recommended by the industry. At 3 wk of age, birds were randomly assigned to a 2 × 3 factorial. The first factor included two species (chickens and turkeys), and the second included doses (0, 4, and 8 mg/mL) of Octanoate in drinking water for 30 d. Feed and WI were recorded daily, while body weight and blood samples were obtained weekly. In chickens, Octanoate doses increased ghrelin and BHB concentrations linearly, while FI and BW decreased linearly with rising Octanoate doses (P < 0.05). However, Octanoate doses did not affect ghrelin, BHB, FI, or BW in turkeys. In conclusion, our data indicate that sodium octanoate administration elicits a differential response in feed intake and body weight gain in chickens and turkeys.

Covalent adduct formation of histone with organophosphorus pesticides in vitro

It is established that organophosphorus pesticide (OPP) toxicity results from modification of amino acids in active sites of target proteins. OPPs can also modify unrelated target proteins such as histones and such covalent histone modifications can alter DNA-binding properties and lead to aberrant gene expression. In the present study, we report on non-enzymatic covalent modifications of calf thymus histones adducted to selected OPPs and organophosphate flame retardants (OPFRs) in vitro using a bottom-up proteomics method approach. Histones were not found to form detectable adducts with the two tested OPFRs but were avidly modified by a few of the seven OPPs that were tested in vitro. Dimethyl phosphate (or diethyl phosphate) adducts were identified on Tyr, Lys and Ser residues. Most of the dialkyl phosphate adducts were identified on Tyr residues. Methyl and ethyl modified histones were also detected. Eleven amino residues in histones showed non-enzymatic covalent methylation by exposure of dichlorvos and malathion. Our bottom-up proteomics approach showing histone-OPP adduct formation warrants future studies on the underlying mechanism of chronic illness from exposure to OPPs.

Exploring the Molecular Docking Interactions between the Polyherbal Formulation Ibadhychooranam and Human Aldose Reductase Enzyme as a Novel Approach for Investigating its Potential Efficacy in Management of Cataract

Background: Kannir sirandha urupillai... which means no organ is better than eye. Eye health and treatment have held significant importance in the Siddha system of medicine since ancient times, emphasizing the holistic approach to well-being encompassing physical, mental, and spiritual aspects. Eye disease is classified into 96 types and their ethology, treatment method, preventive measures all are explained in many of the Siddha literature. Among them cataract is one of the leading cause of blindness which is characterised by clouding of eye’s natural lens, leading to blurry, foggy or flimy vision. This paper will elaborates about the docking analysis of poly herbal formulation Ibadhy chooranam against Human aldose reductase enzyme for cataract.  Aim &amp; Objective: The aim of this study is to investigate the potential efficacy of the polyherbal formulation IbadhyChooranam in preventing or treating cataracts through molecular docking analysis of its interactions with the human aldose reductase enzyme.  Methodology: Docking simulations were conducted for the extracted phytoconstituents of IbadhyChooranam against the Human Aldose Reductase Enzyme. AutoDock tools were utilized to incorporate hydrogen atoms, Coleman united atom type charges, and solvation parameters. The docking process employed the Lamarckian genetic algorithm along with the Solis &amp; Wets Local Search method to simulate ligand-receptor interactions.  Result: The current study revealed that phytochemicals present in IbadhyChooranam, including Nerolidol, Ellagic acid, Phyllanthin, Costunolide, Embelin, Cyperolone, Zingiberene, Piperic acid, Piperine, and Lupeol, exhibited between 6 to 9 significant interactions with residual amino acids in the aldose reductase enzyme. In comparison, the standard drug Epalrestat demonstrated 8 viable interactions with the residual amino acids of the aldose reductase enzyme.  Conclusion: According to the computational analysis findings, it can be inferred that the bioactive compounds present in IbadhyChooranam exhibit notable binding affinity towards the target aldose reductase enzyme. Ibadhy chooranam inhibit the function of aldose reductase enzyme which delay the sorbitol accumulation and subsequent cataract development. Through this study, it was also justified that the Ibadhy chooranam possess significant anti-cataract activity.

Cytochrome b5 diversity in green lineages preceded the evolution of syringyl lignin biosynthesis.

Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin-producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms.

Investigations of Ni(II)Cysteine-Tyrosine Dithiocarbamate Complex: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, and Anticancer Activity on MCF-7 Breast Cancer Cell Line.

Breast cancer ranks second in terms of the highest number of cancer deaths for women worldwide and is one of the leading causes of death from cancer in women. The drug that is often used for chemotherapy is cisplatin. However, cisplatin drugs have a number of problems, including lack of selectivity, unwanted side effects, resistance, and toxicity in the body. In this work, we investigated Ni(II) cysteine-tyrosine dithiocarbamate complex against breast cancer. Research on the new complex compound Ni(II) cysteine-tyrosine dithiocarbamate have several stages including synthesis, characterization, in-silico and in-vitro testing of MCF-7 cells for anticancer drugs. The synthesis involved reacting cysteine, CS2, KOH and tyrosine with Mn metal. The new complex compound Ni(II) cysteine-tyrosine dithiocarbamate has been synthesized, characterized, and tested in vitro MCF-7 cells for anticancer drugs. Characterization tests such as melting point, conductivity, SEM-EDS, UV Vis, XRD, and FT-IR spectroscopy have been carried out. The synthesis yielded a 60,16%, conversion with a melting point of 216-218 oC and a conductivity value of 0.4 mS/cm. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting at a sample concentration of 250 µg/mL and an IC50 value of 618.40 µg/mL. Molecular docking study of Ni(II) cysteine-tyrosine dithiocarbamate complex identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α showing active site with acidic residue amino E323, M388, L387, G390 and I389. Hydrophobic and hydrophobic bonds are seen in Ni(II) cysteine-tyrosine dithiocarbamate - Estrogen α has a binding energy of -80.9429 kJ /mol. there were 5 residues responsible for maintaining the ligand binding stable. The compound had significant Hbond contact intensity, however, it was not strong enough to make a significant anticancer effect. Though the synthesized compound shows low bioactivity, this research is expected to give valuable insight into the effect of molecular structure on anticancer activity.

Influence of Aza-Glycine Substitution on the Internalization of Penetratin.

The cell-penetrating peptide (CPP) penetratin has gained much attention over many years due to its potential role as a transporter for a broad range of cargo into cells. The modification of penetratin has been extensively investigated too. Aza-peptides are peptide analogs in which one or more of the amino residues are replaced by a semicarbazide. This substitution results in conformational restrictions and modifications in hydrogen bonding properties, which affect the structure and may lead to enhanced activity and selectivity of the modified peptide. In this work, the Trp residues of penetratin were substituted by aza-glycine or glycine residues to examine the effect of these modifications on the cellular uptake and the internalization mechanism. The substitution of Trp48 or Trp48,56 dramatically reduced the internalization, showing the importance of Trp48 in cellular uptake. Interestingly, while aza-glycine in the position of Trp56 increased the cellular uptake, Gly reduced it. The two Trp-modified derivatives showed altered internalization pathways, too. Based on our knowledge, this is the first study about the effect of aza-amino acid substitution on the cell entry of CPPs. Our results suggest that aza-amino acid insertion is a useful modification to change the internalization of a CPP.