PASS Online Research Articles

Characterization, quantification and a multi-computational in silico toxicity assessment of impurity (feruloyl methane) in synthetic curcumin using RP-HPLC-UV technique

Feruloyl Methane (FM) is a common impurity in Synthetic Curcumin (SC) that affects its purity and potency. The identification and quantification of FM is crucial to ensure the quality and safety of SC based drugs. The current study aims to develop and validate a simple, rapid and cost-effective analytical technique for the precise and accurate quantification of FM in SC using RP-HPLC with a UV-Vis detector (Ultraviolet/Visible) and assessment of its toxicity by multi-computational methods. The developed HPLC method with a UV-Vis detector enabled accurate identification and quantification of FM in SC. The optimized method was validated in accordance with ICH guidelines Q2(R1) and all parameters were found to be within the standard acceptance range. The ideal run time was determined to be 10 min and the impurity eluting at a retention time of 2.65 min was characterized using spectral techniques viz., mass spectrometry, FTIR and 1 H NMR, confirming the presence of FM. The amount of FM in SC was estimated to be 8.26 µg/kg. In addition, toxicity assessments using in silico tools such as ProTox- II, ADMETlab 2.0 and PASS Online indicated that the presence of FM in SC is not safe for human consumption. In conclusion, the developed method is not only capable of quantifying FM but also aids in distinguishing Natural Curcumin (NC) adulterated with SC and can be applied to a wide range of fields such as natural drug analysis, food analysis and toxicity prediction.

The potential of Myricitrin, a Flavonoid Compound in Eugenia polyantha from Indonesia, as an Antiviral Drug for SARS-Cov-2 through the Molecular Docking Analysis

A Flavonoid glycoside compound, isolated and identified from E. polyantha as myricitrin, was analyzed as a ligand for its molecular binding activity against SARS-CoV-2 protein (receptor binding domain on Spike/RBD, main protease/nsp5, EndoRNAse, RNA-dependent-RNA-polymerase/RdRp), and its receptor, ACE2, and computationally assessed via molecular docking method. This study aims to determine the potential of myricitrin in E. polyantha from Indonesia as an antiviral drug for SARS-CoV-2 through molecular docking and molecular dynamic simulation analysis. The results showed that the myricitrin had the strongest binding affinity energy towards the three important SARS-CoV-2 proteins, namely endoRNAse, main protease (3CLpro), and RdRp with ∆G values of −9.60 kcal/mol, −8.40 kcal/mol, and −8.30 kcal/mol, respectively. These values are stronger than the comparator ligands of favipiravir (−5.60 kcal/mol), atazanavir (−7.20 kcal/mol), and remdesivir (−7.70 kcal/mol). This indicated that the compound has the potential as an inhibitor against 3CLpro, endoRNAse, and RdRp of SARS-CoV-2 proteins. This result was supported by the prediction made according to the Molprobity and PASS Online web servers, which showed that myricitrin has high bioactivity potential as an enzyme inhibitor (with a score of 0.38) and antiviral (with a score of 0.704).

Molecular docking studies of Brucein D as a potential inhibitor of the Bcl-2 anti-apoptotic protein

Link of Video Abstract: https://youtu.be/JOzTSty10v4Background: Brucein D (BrD), a quassinoid isolated from Brucea javanica fruit, reportedly demonstrates anti-tumor activity. Bcl-2 is an anti-apoptotic protein that inhibits apoptosis and leads to cancer progression. This study aims to evaluate the inhibitory effect of BrD against the anti-apoptotic protein Bcl-2 by molecular docking study. Methods: We investigated the activity of BrD against Bcl-2 through molecular docking in silico compared to the chemotherapeutic drugs doxorubicin and docetaxel. Molecular docking analysis was conducted using the Lipinski rule of five drug-likeness analyses, PASS Online prediction, PyRx v0.8, Discovery Studio DS BIOVIA 2016 v16, and PyMol v2.4. Results: Current results show that BrD is qualified as a drug and can pass cell membranes without toxicity. The PASS prediction also shows that BrD can be activated as an anti-neoplastic inside the human body with Pa higher than Pi. BrD can make a constant and stable bond to Bcl-2 with a binding energy of -8.3 kcal/mol, almost equal to doxorubicin and docetaxel. BrD can form six types of hydrogen bonds that show stability to temperature and pressure. Conclusion: BrD has shown to be a promising alternative for an anti-cancer drug by inhibiting the Bcl-2 anti-apoptotic protein with low toxicity in normal cells.

Molecular docking, QTAIM analysis, UV-Vis spectra, vibrational analysis, and electronic properties of Lantadenes C and D — A complete comparative study

We have done geometry optimization of two conformers of Lantadene series C and D. The fundamental vibrational frequencies with intensity have been done by using B3LYP/6-311G (d, p) method. The complete vibrational assignments of wavenumbers are made on the basis of potential energy distribution (PED). The nonbonding interactions in Lantadenes C and D are calculated by using the same level theory at the bond critical point (BCP). The calculated topological parameters at BCP are utilized to determine the nature and strength of interactions. We have also computed HOMO–LUMO gap and plotted frontier orbital HOMO–LUMO surfaces, molecular electrostatic potential surfaces to explain the reactive nature of Lantadenes C and D. The electronic transition spectra UV–Vis spectra of Lantadenes C and D are calculated by using TDDFT theory. The values of hyperpolarizability show a probable use of these compounds in electro-optical applications. The natural bonding orbital theory is utilized to calculate transition of electron from donor to acceptor which is very useful to describe nonbonding as well as bonding interactions. The calculated value of Log [Formula: see text] and Log [Formula: see text] for Lantadene C Lantadene D established its pharmaceutical behaviors. The biological activity of Lantadenes C and D is also calculated by using PASS online server for [Formula: see text]. The docking of Lantadene C Lantadene D is also performed by using Auto dock with predicted drug by Swiss dock online server.

Potential of fenugreek (Trigonella foenum-graecum L.) metabolites as dental residual ridge resorption inhibitors through estrogen receptor signaling: In silico study

Context: Edentulism is a global health burden with long-life disabilities. Dental implant procedures are frequently constrained to alveolar residual ridge resorption. The resorption is strongly correlated with an imbalance of osteoblast-osteoclast activities. Estrogen well established maintain bone homeostasis. Fenugreek (Trigonella foenum-graecum L.) is a promising drug candidate to promote estrogenic activity and resist residual ridge resorption. Aims: To evaluate the drug-likeness, pharmacokinetic, toxicity as well as molecular interaction prediction between T. foenum-graecum metabolite compounds and estrogen receptor-α (ESRα)/estrogen receptor-ß (ESRß). Methods: The drug-likeness was evaluated using Lipinski's rule of five. A web server (PkCSM) was used to predict the pharmacokinetics and toxicity. The metabolites were retrieved from the Kanaya database. The biological activity prediction was performed using PASS Online. The ligands’ structures were downloaded from PubChem National Centre for Biotechnology Information database. Proteins were obtained from Protein Data Bank. Molecular docking prediction was carried out using PyRx software and visualized using Discovery Studio Software. Results: Quercetin, naringenin, luteolin, and kaempferol displayed the highest biological activity of estrogen agonist, anti-inflammatory, and tumor necrosis factor (TNF) expression inhibitor. Four metabolites exhibited the potential to be developed as oral drugs with good absorption in gastrointestinal, moderate tissue distribution, and safe for liver tissue. Quercetin and kaempferol showed the most negative value of binding affinity. Quercetin formed three hydrogen bonds and eight hydrophobic bonds with ESRα. Luteolin had three hydrogen bonds and five hydrophobic bonds on ESRβ. Conclusions: Metabolites present in T. foenum-graecum, like quercetin, naringenin, luteolin, and kaempferol, were potential drug candidates that could act as estrogen agonists to inhibit the dental residual ridge resorption.

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol.

Alternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for alternariol and its metabolites using an in silico working model based on the MetaTox, SwissADME, pKCMS, and PASS online computational programs. A number of 12 metabolites were identified as corresponding to the metabolomic profile of alternariol. ADME profile for AOH and predicted metabolites indicated a moderate or high intestinal absorption probability but a low probability to penetrate the blood-brain barrier. In addition to cytotoxic, mutagenic, carcinogenic, and endocrine disruptor effects, the computational model has predicted other toxicological endpoints for the analyzed compounds, such as vascular toxicity, haemato-toxicity, diarrhea, and nephrotoxicity. AOH and its metabolites have been predicted to act as a substrate for different isoforms of phase I and II drug-metabolizing enzymes and to interact with the response to oxidative stress. In conclusion, in silico methods can represent a viable alternative to in vitro and in vivo tests for the prediction of mycotoxins metabolism and toxicity.

In-vitro and in-silico evaluation of Brugmansia sauveolens' ability to treat asthma

Asthma is a common chronic inflammatory disease of the airways. The airway epithelium produces bioactive cellular mediators that trigger the chronic inflammatory response. These mediators then attract and activate inflammatory cells in the airways of the lungs and release more biochemical mediators. With several benefits, such as a significant reduction in the cost and time of drug discovery as well as the use of laboratory animals, in-silico studies have grown to be an important and simple method for examining various chemical compounds against various targets. One of the common herbs found in the local Himalayan area is Brugmansia sauveolens, known as Datura, which is a source of tropane alkaloids and asthma can be effectively managed with alkaloids. Using a Soxhlet extractor, the collected plant components were first extracted with petroleum ether (to remove fats) followed by methanol. Online technologies like PASS Online, Molinspiration, SEA, SWISS, and SLAP data were used for a variety of in-silico predictions. After that, we tested the ability of Brugmansia extracts to reduce inflammation using an in-vitro approach. Rat RBC membrane lyses were stabilized using the plant extract fractions. The outcomes were also compared with aspirin (a common anti-inflammatory drug). Bioinformatics techniques were used to detect structural activity. After investigating all the data It was shown that B. sauveolens had anti-asthmatic activity.

Bioactive Xanthone C-glycoside Derivatives – QSAR Approach

Introduction. Xanthone glycosides have unique structures and properties. Many efforts focus on the search for C-glycoside derivatives of mangiferin with higher bioavailability. The application of the QSAR approach allows for the optimization of the search for novel xanthone derivatives with the desired characteristics.Aim. Using available descriptors of chemical structure, physical-chemical properties, and biological activity, analyze a sample set of known homologs and analogs of mangiferin to QSAR prognosis bioactivity of new xanthone C-glycosides.Materials and methods. 26 molecules of natural homologs and modified derivatives of mangiferin formed the analyzed sample set. Topological graphs of compounds were constructed using ChemicPen software. ChemicDescript software was used for the calculation of molecular descriptors, including the Balaban index. Physicochemical characteristics of molecules as well as Lipinski's rule criteria were calculated in Molinspiration. The spectrum of the most probable (Pa > 0.7) biological activity of the described compounds were predicted using Pass Online. The software Origin (OriginLab, USA) was used for the graphical representation of the results.Results and discussion. Mangiferin and its natural homologs are the most hydrophilic compounds. The hydrolysis of the C-glycosidic bond, alkylation, acylation, and the introduction of an amino substituent radical into the mangiferin structure led to the increase of its lipophilic properties. The spectrum of the most probable biological activities of the described molecules: antitumor, antioxidant, and cardioprotective effects. The results of ADMET modeling based on the substance-drug similarity criteria showed that only 4 compounds correspond to the rule of five. We proposed the validation model to predict bioactivity from lipophilicity and molecule structure described with Balaban index. The error of prediction obtained in a result of cross-validation turned out to be about less than 3 %.Conclusion. A correlation between the structure and properties of the molecules discussed has been demonstrated. The obtained results can be used for further prediction of the properties of natural and synthetic xanthone C-glycosides and directed synthesis of new active compounds.

Screening of Rhodomyrtus tomentosa (Aiton) Wight (Karamunting) Compounds that Have the Potential for Breast Cancer

Breast cancer is the highest disease in the world beating lung cancer, so various alternatives are needed to find a treatment. Screening drug discovery against breast cancer by targeting BCL-2 occupies the main position and is the goal of this study. The method used is insilico. the material used is 10 compounds from R. tomentose, 2w3l protein from RCSB, PLANT docking software, the docking coordinate used is X: 39.8057 Y: 26.9355 Z: -12.4145 with a radius of 11.1871, then to find out the type of bond and residue involved using discovery studio. The results of this study were docking scores from -91.3871(5'-Desgalloylstachyurin) to -65.4754 (Afrormosin), activity predictions from PASS online from 0.174 (Rhodomyrtosone C) to 0.799 (Lupeol). Based on the docking score, three compounds that have the potential to inhibit the work of BCL-2 were obtained namely 5'-Desgalloylstachyurin, Rhodomyrtosone B and Rhodomyrtosone D.

Thymol and eugenol against Rhipicephalus sanguineus sensu lato engorged females: Biological, histopathological and bioinformatic analysis

The aim of this study was to evaluate the reproductive biology and histopathology of the ovaries of engorged females of Rhipicephalus sanguineus sensu lato exposed to combinations of thymol and eugenol, as well as to evaluate in silico the possible interactions of thymol and eugenol in tick cell membranes. To evaluate the tick reproductive biology, the adult immersion test (AIT) was performed, in which the engorged females were immersed in solutions of thymol and eugenol, combined or alone, at concentrations of 2.5 and 5.0 mg/mL. Two control groups (water and 3% DMSO) were also performed. The ticks were kept in a controlled chamber (B.O.D - 27 ± 1 °C and 80% ± 5% RH) to evaluate egg production and viability. To perform the ovaries histopathological evaluation, females were immersed in combination of thymol and eugenol (each at 2.5 and 5.0 mg/mL) and control (water and 3% DMSO) solutions. After immersion, the females were kept in B.O.D (27 ± 1 °C and RH of 80% ± 5%) for four days, they were dissected and the ovaries processed for histological analysis. In addition, an in silico analysis was performed using PASS online® software to predict probability activity (PA) of thymol and eugenol in cell membranes. The treatment with the combination of thymol and eugenol (each at 5.0 mg/mL) caused a reduction (p < 0.01) in oviposition, while the treatments with thymol (5.0 mg/mL) and combination of thymol and eugenol (5.0 mg/mL) reduced (p < 0.05) the egg viability. The treatment with combination of thymol and eugenol (5.0 mg/mL) resulted in a control percentage of 99.9%, while in the other treatments, control percentages below 56% were observed. Oocytes from the females exposed to the combinations of thymol and eugenol (each compound at 2.5 mg/mL) showed histopathological changes, except on oocyte V, while those treated with these compounds alone at 2.5 mg/mL, did not reveal any change. Changes in the shape of the oocyte, presence of vacuoles in the cytoplasm and germinal vesicle, reduction and fusion of yolk granules and rupture of some oocytes were observed. In silico analysis, showed that these compounds can act as membrane permeability inhibitors, membrane permeability agonists, membrane integrity antagonists and apoptosis agonists. We conclude that the combination of thymol and eugenol causes changes in the reproductive biology and morphophysiology of engorged females oocytes. The in silico analysis using thymol and eugenol revealed the possibility of disorganization in the cell membranes, a fact that may explain the histopathological alterations observed.

3a-(4-Chlorophenyl)-1-methyl-3a,4-dihydroimidazo[1,5-a]quinazolin-5(3H)-one: Synthesis and In Silico Evaluation as a Ligand in the µ-Opioid Receptor

In the search for fused heterocycle molecules with potential biological activities, the new title compound was produced in racemic form via a four step-synthetic sequence with an overall yield of 60%. It was structurally characterised via 1H-, 13C-NMR and IR analyses, and the molecular composition was confirmed through a high-resolution MS experiment. After predicting its analgesic activity using PASS online software, wherein a good overlap between its enantiomers and the structure of the natural opioid morphine was observed, the compound was evaluated through docking calculations as a ligand of the µ-opioid receptor. The resulting energy values and interactions were comparable to the data obtained for morphine and its synthetic derivative fentanyl, which is used in the therapeutic treatment of severe forms of pain. Moreover, the title compound displayed favourable predicted blood–brain barrier permeation and drug-likeness.

Molecular Docking of the Cannabis sativa L. Bioactive Compound Against Inflammation Induced by Cigarette Smoke Exposure

Cigarette smoke can modulate and increase chronic inflammation of the respiratory tract. The constituents of cigarette smoke-induced inflammation can activate several cell signaling pathways, including mitogen-activated protein kinases (MAPK), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription (STAT), and activatory protein-1 (AP-1). Cannabis plant (Cannabis sativa L.) contains many phytochemical compounds including cannabinoids, terpenes and phenolic compounds, which have potential in medicine, one of them is as an anti-inflammatory. This study aims to determine the interactions formed between bioactive compounds from cannabis plants in anti-inflammatory activity caused by cigarette smoke induction in the JAK/STAT and MAPK pathways through a study in silico. This research method was carried out in a descriptive exploratory manner using online databases such as PubChem, PASS online, SEA (Similarity Ensemble Approach) and Swiss Target Prediction, STRING. Docking simulation was carried out using PyRx 0.8. Data from software and web devices were analyzed descriptively and compared with control compounds. The docking results show that the compounds from Cannabis sativa L. can act as an anti-inflammatory in the context of cigarette smoke-induced inflammation. This is indicated by the similarity of amino acid residues resulting from the interaction of the aspirin drug (control) with the anti-inflammatory receptor protein in the compound cannabidihydrophenanthrene with PDGFRA and KDR receptors and compounds cannabicyclol with AKT1 and KDR receptors. This is indicated by the presence of value affinity is low indicating a stable and strong bond.

Kajian in Silico Daun Sungkai (Peronema canescens) dalam Menghambat Enzim lanosterol 14-α demethylase Jamur Candida albicans

Candida albicans (C. albicans) is a fungus that causes candidiasis. C. albicans has the enzyme Lanosterol 14- α demethylase. Lanosterol 14-α-demethylase has bioactivity in converting lanosterol to ergosterol, a special sterol found in fungal membranes, which mediates membrane permeability and fluidity. One way to treat candidiasis is to use traditional medicinal plants. Sungkai (Peronema canescens) can be used as an anti-fungal medicine. Drug development efforts can be done using the In silico method. Objectives of this study was to determine the interaction between terpenoid, flavonoid, and phenol compounds in Sungkai leaves against Lanosterol 14-α demethylase in Candida albicans. The research design used was a pre-experimental one-shot case study. Toxtree software was used to test the toxicity of compounds. Test for compound potency using the Pass Online webserver. Docking molecular using PyRx software. Visualization of docking results using Discovery Studio 2019 Software. Physicochemical test of compounds using Lipinski Test. The results showed that the compounds that had a low risk of toxicity were butanoic, catechol, guaiacol, hydroquinone, isopropanol, methanoic acid, palmitic acid, and phytol. Compounds that have anti-fungal activity based on Pharma-expert analysis are butanoic acid, genkwanin, guaiacol, hydroquinone, isopropanol, palmitic acid, and phytol. Compounds that have hydrogen bonds and binding affinity value 10 and RMSD value 2 are butanoic acid, catechol, genkwanin, guaiacol, hydroquinone, isopropanol, methanoic acid, palmitic acid, and quinic acid compounds. These compounds are thought to inhibit the Lanosterol 14-alpha demethylase enzyme in C. albicans. Compounds that comply with Lipinski's rules are anthocyanin and genkwanin compounds. The groups of compounds found in Sungkai leaves that have antifungal activity are the terpenoids, flavonoids, and phenols.

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study.

Little is known about the metabolomic profile of quercetin and its biological effects. This study aimed to determine the biological activities of quercetin and its metabolite products, as well as the molecular mechanisms of quercetin in cognitive impairment (CI) and Parkinson's disease (PD). Key methods used were MetaTox, PASS Online, ADMETlab 2.0, SwissADME, CTD MicroRNA MIENTURNE, AutoDock, and Cytoscape. A total of 28 quercetin metabolite compounds were identified by phase I reactions (hydroxylation and hydrogenation reactions) and phase II reactions (methylation, O-glucuronidation, and O-sulfation reactions). Quercetin and its metabolites were found to inhibit cytochrome P450 (CYP) 1A, CYP1A1, and CYP1A2. The studied compounds demonstrated significant gastrointestinal absorption and satisfied Lipinsky's criterion. Due to their high blood-brain barrier permeability, P-glycoprotein inhibition, anticancer, anti-inflammatory, and antioxidant capabilities, quercetin and its metabolite products have been proposed as promising molecular targets for the therapy of CI and PD. By regulating the expression of crucial signaling pathways [mitogen-activated protein kinase (MAPK) signaling pathway, and neuroinflammation and glutamatergic signaling], genes [brain derived neurotrophic factor (BDNF), human insulin gene (INS), and dopamine receptor D2 (DRD2), miRNAs (hsa-miR-16-5p, hsa-miR-26b-5p, hsa-miR-30a-5p, hsa-miR-125b-5p, hsa-miR-203a-3p, and hsa-miR-335-5p], and transcription factors [specificity protein 1 (SP1), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and nuclear factor Kappa B subunit 1 (NFKB1)], quercetin exhibited its neurotherapeutic effects in CI and PD. In addition to inhibiting β-N-acetylhexosaminidase, quercetin also showed robust interactions and binding affinities with heme oxygenase 1 (HMOX1), superoxide dismutase 2 (SOD2), tumor necrosis factor (TNF), nitric oxide synthase 2 (NOS2), brain-derived neurotrophic factor (BDNF), INS, DRD2, and γ-aminobutyric acid type A (GABAa). This study identified 28 quercetin metabolite products. The metabolites have similar characteristics to quercetin such as physicochemical properties, absorption, distribution, metabolism, and excretion (ADME), and biological activities. More research, especially clinical trials, is needed to find out how quercetin and its metabolites protect against CI and PD.

In Silico Analysis and ADMET Prediction of Flavonoid Compounds from Syzigium cumini var. album on α-Glucosidase Receptor for Searching Anti-Diabetic Drug Candidates

Background: One of the causes of death is diabetes. Anti-diabetic drugs currently available do not work optimally because some have been reported to have side effect and resistance. Objective: This study aimed to flavonoid compounds from Syzygium cumini var. album with the greatest anti-diabetic activity and lower toxicity than acarbose. Materials and Methods: This research is an in silico study of nine flavonoid compounds from Syzygium cumini var. album, starting with PASS online was used to predict the activity spectrum of substances, drug-likeness prediction using DruLiTo, ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) using pkCSM online. Molecular docking was carried out by the AutoDock 4.2.6 program on α-glucosidase targeting. Visualization is done with the Discovery Studio Visualizer software. Results: From the data obtained, D-(+)-Catechin has a high affinity for α-glucosidase with a free energy of binding (ΔG) -5.94 kcal/mol and an inhibition constant (Ki) of 44270 nm. Conclusion: Based on the results of the study, it can be concluded that the flavonoid compounds from Syzygium cumini var. album has the potential as a promising anti-diabetic drug candidate, where the best candidate is D- (+)-Catechin. However, further studies of flavonoid compounds from Syzygium cumini var. album are needed.

In Silico Study on Anti-inflammatory Effect of Bioactive Compounds of Velvet Bean (Mucuna pruriens) Leaves Against NF-kB Activation Pathway

Activation of nuclear factor-kB (NF-ĸB) receptors potently enhances pro-inflammatory cytokines production thereby promoting inflammatory reactions. NF-ĸB receptor inhibition is one of the targets in overcoming inflammatory reactions. One of the natural ingredients that have the potential as an anti-inflammatory is velvet bean leaf extract (Mucuna pruriens L. (DC.)) which is used by the local people of West Sumatra. This study aimed to investigate the anti-inflammatory mechanism of the bioactive compounds detected in velvet bean leaf extract against NF-ĸB (1U36) activation pathway using an in silico approach. The phytochemical analysis of the ethanolic extract of velvet bean leaves was performed using GC-MS. Subsequently, their potential bioactivities were explored using PASS online test, preparation of ligands, receptors, and molecular docking. The results showed that the 34 compounds contained in the miang bean leaf extract had anti-inflammatory bioactivity with a probability activity value of &gt;0.7 based on PASS online. The docking results showed that the highest binding affinity value was found in artemin (-7.5 kcal/mol) which was higher than the standard anti-inflammatory drug ketoconazole (-7.2 kcal/mol). Therefore, one of the mechanisms of miang bean leaves as an anti-inflammatory is due to the inhibitory action of artemin on the NF-kB activation pathway.

A curcumin-nicotinoyl derivative and its transition metal complexes: synthesis, characterization, and in silico and in vitro biological behaviors.

Curcumin-nicotinoyl (Cur-Nic) was synthesized by the chemical modification of the curcumin structure, characterized, and used as a ligand for the synthesis of copper(II) and zinc(II) complexes. The biological activities of Cur-Nic and its metal complexes were predicted using the PASS and Swiss Target Prediction online software, respectively, and docking studies with tyrosine-protein kinase SRC were performed using the PyRx software to predict their anticancer activities. The toxicity effects of the complexes on a human breast cancer cell line (MCF-7) compared to a healthy breast cell line (MCF-10A) were investigated by the MTS assay. Although the metal complexes maintained the least toxicity against normal cells, the results indicated that compared to curcumin and Cur-Nic, the cytotoxicity toward cancer cells increased due to the complexation process. Moreover, the antibacterial evaluation of the compounds against a Gram-positive bacterium (MRSA) and a Gram-negative bacterium (E. coli) indicated that the Cu(II) complex and Cur-Nic were the best, respectively. Also, the Zn(II) complex was the most stable compound, and the Cu(II) complex was the best ROS scavenger based on the in vitro evaluation.

Green Synthesis, Characterization, In Silico ADMET Profiling, Molecular Docking Studies of 3, 4-Dihydropyrimidin-2-(1H)-ones Against Voltage-Gated Calcium Channel (4MS2) Receptor

The present work involves design, synthesis and evaluation of derivatives of 3,4-dihydropyrimidine 2 one. Using pyrimdine as a core structure for design of novel pyrimidine derivatives which are calcium channel blocker, Derivatives of 3,4-dihydropyrinidine-2-one was synthesized by microwave assisted synthesis method. There are ten derivatives are synthesized by microwave assisted synthesis in laboratory. The entire synthesized compound was tested using Insilco parameters like Pass online data, SwissADME parameters and toxicity parameters by using protox II. All the synthesized compound tested by pass online software for its biological activity. All the synthesized compounds reflelects various activities like antihypertensive, antianginal, antiviral, antifungal and all of them are calcium channel blockers.

Limoniastrum monopetalum-Mediated Nanoparticles and Biomedicines: In Silico Study and Molecular Prediction of Biomolecules.

An in silico approach applying computer-simulated models helps enhance biomedicines by sightseeing the pharmacology of potential therapeutics. Currently, an in silico study combined with in vitro assays investigated the antimicrobial ability of Limoniastrum monopetalum and silver nanoparticles (AgNPs) fabricated by its aid. AgNPs mediated by L. monopetalum were characterized using FTIR, TEM, SEM, and DLS. L. monopetalum metabolites were detected by QTOF-LCMS and assessed using an in silico study for pharmacological properties. The antibacterial ability of an L. monopetalum extract and AgNPs was investigated. PASS Online predictions and the swissADME web server were used for antibacterial activity and potential molecular target metabolites, respectively. Spherical AgNPs with a 68.79 nm average size diameter were obtained. Twelve biomolecules (ferulic acid, trihydroxy-octadecenoic acid, catechin, pinoresinol, gallic acid, myricetin, 6-hydroxyluteolin, 6,7-dihydroxy-5-methoxy 7-O-β-d-glucopyranoside, methyl gallate, isorhamnetin, chlorogenic acid, 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-β-l-mannopyranosyl)-β-d-glucopyranoside) were identified. The L. monopetalum extract and AgNPs displayed antibacterial effects. The computational study suggested that L. Monopetalum metabolites could hold promising antibacterial activity with minimal toxicity and an acceptable pharmaceutical profile. The in silico approach indicated that metabolites 8 and 12 have the highest antibacterial activity, and swissADME web server results suggested the CA II enzyme as a potential molecular target for both metabolites. Novel therapeutic agents could be discovered using in silico molecular target prediction combined with in vitro studies. Among L. Monopetalum metabolites, metabolite 12 could serve as a starting point for potential antibacterial treatment for several human bacterial infections.

Evaluation of anticancer activities, apoptosis, molecular docking, and antioxidant studies of new Ni(II), VO(IV), Cu(II) and Co(III) Schiff base complexes

New Schiff base complexes have been synthesized via appropriate conventional methods using 2-ethoxy-6-(E)-[(prop-2-em-1-yl)imino]methylphenol (HL) as a Schiff base ligand. The compounds obtained were characterized by spectral analysis and X-ray diffraction. Recrystallization from methanol provided single crystals with rod-shaped (1) and rhombus-shaped (2) shapes. The complexes were found to be composed of NiL2 and (VO)L2, with the anionic ligand L- acting as a bidentate ligand, coordinating to metal centers via imino N and hydroxyl oxygen atoms in all cases. Compound (1) crystallizes in the orthorhombic system with the Pccn space group, while compound (2) crystallizes in the monoclinic system with the P21/n space group. Cyclic voltammetry experiments in DMF show a metal-centered reduction peak at (−1.23), (−1.32), (−0.82, 1.36), and (−0.61, −1.55) V, corresponding to the Ni II/NiI, VO2+/VO+, CuII/CuI, and CoIII/II-CoII/I, respectively. The complexes were evaluated for anticancer activity in a human tumor cell line (HT-29). 5-fluorouracil was used as a standard drug. All tested compounds of Schiff base ligand and complexes (1–4) showed anticancer activity with inhibitory concentration (IC50) values of 85.28(HL), 15.13(1), 10.83(2), 28.53(3) and 30.21(4) (μM), respectively. The in vitro cytotoxicity screening results revealed that all compounds showed promising activity against colorectal cancer. In particular, compounds (1) and (2) showed excellent activity against tumor cell lines. The antioxidant activity of the synthesized Schiff base was determined using the DPPH method (1, 1-diphenyl-2- picryl hydrazyl). The effective concentration (EC50) indicates that all compounds have good antioxidant activity (EC50 = 143.02(HL), 168.03(1), 27.31(2), 160.3(3) and 173.41(4). The biological activity spectra of synthesized compounds are predicted by the Pass Online Web Resource. In addition to the PASS program's prediction, molecular docking studies were also performed to find bind affinity to protein cyclooxygenase inhibitor (the structure PDB code 1CX2).