Minimum Binding Energy Research Articles

Synthesis, spectroscopic, computational, topology, and molecular docking studies on N,N'-(4-methyl-1,3-phenylene)bis(1-(2,4-dichlorophenyl)methanimine)

The study extensively examined N,N'-(4-methyl-1,3-phenylene)bis(1-(2,4-dichlorophenyl)methanimine) (6D). Advanced spectroscopic techniques, including IR, Raman, NMR, and UV-VIS spectroscopies, were employed to analyse the molecule. The Schiff base was ultimately confirmed using NMR spectrum analysis. The UV-VIS study revealed a notable bathochromic change in the compound, indicating their electronic transitions. By using the HOMO–LUMO bond gap the titled compound reactivity sites were identified. The compound 6D HOMO–LUMO band gap is 3.70 eV. Various wave function investigations like MESP, HOMO–LUMO, RDG, ELF, LOL, and ALIE were conducted to elucidate the distribution of electronic charge, providing valuable insights into the behaviour of molecules. The biological probability of the synthesised compound was extensively assessed using a docking study. Using MEP and HOMO–LUMO investigations, we confirm nucleophilic and electrophilic attacking sites. In the docking study, the protein Bovine cytochrome bc1 complex stigma Tellin bound (PDB ID–1PP9) was downloaded. The docking study identified the most stable minimum binding energy is –6.26 kcal/mol.

6-Methoxyflavone improves anxiety, depression, and memory by increasing monoamines in mice brain: HPLC analysis and in silico studies

Abstract 6-Methoxyflavone (6-MOF) is a flavonoid that has been reported to be a GABA-A receptor agonist and reverses cisplatin-induced hyperalgesia and allodynia. Considering the varied neuropharmacological profile of 6-MOF, this study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety, novel object recognition (NOR), depression, spatial memory, socialization behavior, nest-building behavior, and depression in various groups of mice. Selected groups of mice were injected with 25, 50, and 75 mg/kg 6-MOF. Using HPLC-UV, the frontal cortex, striatum, and hippocampus of the sacrificed mice were analyzed for the levels of vitamin C, dopamine, serotonin, noradrenaline, adenosine, and its metabolites. Statistical analysis showed significant results in socialization behavior and elevated plus maze with 75 mg/kg. In Y-maze, NOR 6-MOF showed significant results at all three doses, while in tail suspension test (TST), 50 and 75 mg/kg showed significant results; however, no statistical significance was observed in nest-building behavior; 50 and 75 mg/kg 6-MOF showed significant results in the Morris water maze. 6-MOF raised vitamin C levels in the frontal cortex and hippocampus. Serotonin, dopamine, and nor-adrenaline levels were raised in the hippocampus and striatum. It has also imparted region-specific neuroprotection by improving adenosine and its metabolite levels. In silico studies performed using PyRx have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol. The binding energy showed that 6-MOF was successfully docked with an anti-oxidant enzyme. In conclusion, in silico and behavioral studies showed that 6-MOF can be a potential candidate for the treatment of cognitive decline, anxiety, and depression.

Quantum chemical treatment, electronic energy in various solvents, spectroscopic, molecular docking and dynamic simulation studies of 2-amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide: A core of anticancer drug

The titled molecule 2-Amino-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (ANMC) is a core of anticancer drug dasatinib (leukemia). Its derivatives exhibited bioactivity against breast cancer. Experimentally, the titled compound was described using NMR (1H NMR and 13C NMR), FTIR and UV–visible spectroscopy. The results were compared with the theoretical predictions, showing good agreement such as theoretical NH vibrations showed symmetric stretching and asymmetric stretching at 3429 and 3440 cm−1 respectively, λmax values appear at 305 nm for experimental and 307.75 nm for theoretical observations in acetone medium. Hirshfeld surface analysis well described the secondary internal and external interactions obtained like dnorm and di ranges −1.8551 to 1.4590 and 0.0918 to 2.6756 respectively. Comparing UV–visible spectra obtained in various solvents with the calculated TD-DFT results revealed minimal solvent effects. Molecular electrostatic potential (MEP) map and Fukui functions were employed, which indicated reactive sites of the molecule and the obtained order of nucleophilic reactivity was C16 > C2 > C8 > Cl1 > C22 > C21. The bioactivity profile probability of ANMC was theoretically explored by calculation of electrophilicity index and drug-likeness. Molecular docking of the ANMC molecule was performed with ten receptors to obtain the best ligand–protein interaction and the minimum binding energy obtained was −8.0 kcal/mol. Biomolecular stability of ANMC was investigated by Molecular Dynamic Simulation (MDS). And also the analysis of free energies showed strong interactions between the ligand and the protein.

Ni(II)-selenosemicarbazones complexes as promising anticancer and anti-tubercular agents: Synthesis, characterization, molecular docking and binding studies with HSA and ct-DNA

Reaction of nickel(II) acetate with selenosemicarbazones (2-HOxsesc, 3-MeHOxsesc, 6-ClHOxsesc, 3-HIndsesc, 3-AcHIndsesc, 9-HAnsesc, 1-HNapsesc, 2-HNapsesc) in 1:2 (M:L) molar ratio yielded complexes of formula, [Ni(sesc)2] 1–8 (sesc = 2-Oxsesc 1, 3-MeOxsesc 2, 6-ClOxsesc 3, 3-Indsesc 4, 3-AcIndsesc 5, 9-Ansesc 6, 1-Napsesc 7, 2-Napsesc 8).Complexes are characterized using elemental analysis, FTIR, NMR (1H and 13C) spectroscopy and Mass spectrometry. The full optimized energy for 2-HOxsesc and its complex was found through Density Functional Theory calculation using B3LYP level and predicted geometry parameters are compared with literature. Selenosemicarbazones and their complexes were tested for their anti-tuberculosis activity against M. tuberculosis H37RV strain and anticancer activity against PA-1 and DU145cell lines. The anti-TB activity of 3-AcHIndsesc (MIC = 25 μg/mL) got exceptionally enhanced on complexation with Ni(II) (complex 5, MIC = 0.8 μg/mL). Anticancer activity of ligands have got enhanced on complexation with Ni(II) metal ion and best results were obtained in case of complex 5 (PA-1, IC50 =1.28; DU145, IC50 =3.83). The binding constant of 6.5 × 103M-1 and 3 × 104M−1 obtained from absorption spectroscopy (UV–Vis) indicates strong binding of complex 5 with HSA and ct-DNA. The molecular interaction of 3-AcHIndsesc and complex 5 with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) were checked with docking studies. The docking studies with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) gave minimum binding energy of -8.9 Kcal/mol and -7.5 Kcal/mol respectively for complex 5. The docking results are in well agreement with experimental data.

In vitro antibacterial, antioxidant, in silico molecular docking and ADEMT analysis of chemical constituents from the roots of Acokanthera schimperi and Rhus glutinosa

Acokanthera schimperi is a medicinal plant traditionally used for the treatment of wounds, scabies, and malaria. Rhus glutinosa has been also utilized for the management of ectoparasites and hemorrhoids. Silica gel column chromatography separation of CH2Cl2/MeOH (1:1) extract root of A. schimperi afforded oleic acid (1), lupeol (2), dihydroferulic acid (3), acovenosigenin A- 3-O-α-L-rhamnopyranoside (4) and sucrose (5) whereas CH2Cl2/ MeOH (1:1) and MeOH roots extracts of R. glutinosa afforded β-sitosterol (6), (E)-5-(heptadec-14-en-1-yl)-4,5-dihydroxycyclohex-2-enone (7), methyl gallate (8), and gallic acid (9). The structures of the compounds were established using spectroscopic (1D and 2D NMR) and FT-IR techniques. Disc diffusin and DPPH assay were used, respectively, to evaluate the antibacterial and antioxidant potential of the extracts and isolated compounds. MeOH extract root of A. schimperi showed a modest antibacterial effect against E.coli with an inhibition zone (ZI) of 16 ± 0.0 mm compared to ciprofloxacin (ZI of 27.0 ± 0.0 mm). CH2Cl2/MeOH (1:1) and MeOH root extracts of R. glutinosa showed maximum activity against S. aureus with ZI of 17.3 ± 0.04 and 18.0 ± 0.0 mm, respectively. At 5 mg/mL, the highest activity was noted against S. aureus by 8 with ZI of 18.6 ± 0.08 mm. Dihydroferulic acid (3), methyl gallate (8), and gallic acid (9) displayed potent scavenging of DPPH radical with respective IC50 of 10.66, 7.48, and 6.08 µg/mL, compared with ascorbic acid (IC50 of 5.83 µg/mL). Molecular docking results showed that lupeol (2) exhibited strong binding energy of -7.7 and − 10 kcal/mol towards PDB ID: 4F86 and PDB ID: 3T07, respectively, compared to ciprofloxacin (-6.5 and − 7.2 kcal/mole). Towards PDB ID: 1DNU receptor, compounds 3, 8, and 9 showed minimum binding energy of -5.1, -4.8, and − 4.9 kcal/mol, respectively, compared to ascorbic acid (-5.7 kcal/mol). The Swiss ADME prediction results indicated that compounds 2, 3, 8, and 9 obeyed the Lipinksi rule of five and Veber rule with 0 violations. The in vitro antibacterial and antioxidant results supported by in silico analysis indicated that compounds 2, 3, 8, and 9 can potentially be lead candidates for the treatment of pathogenic and free radical-induced disorders.

To Explore the Rule and Mechanism of Traditional Chinese Medicine in the Treatment of Postmenopausal Osteoporosis Based on Data Mining, Network Pharmacology and Molecular Docking Technology

Postmenopausal osteoporosis (PMOP) is an important part of primary osteoporosis, and the current clinical treatment program for PMOP is easily limited by side effects and adverse reactions, so it is particularly important to seek more efficient, safe, and economical drug treatment for PMOP. In recent years, with the change of disease treatment mode and the gradual deepening of Traditional Chinese medicine (TCM) research on PMOP, a review of the literature reveals that there is a huge number of studies on the use of TCM in the treatment of PMOP, but there are no relevant systematic studies on the rules of its formulas and the specific mechanisms by which the core drugs exert their therapeutic effects. Therefore, in this study, we collected a total of 141 formulas used by TCM clinicians to treat PMOP, statistically analyzed their high-frequency medications, Four Qi, Five Flavors, meridians, and efficacies, and analyzed the core medications based on the association rules, which were Rehmanniae Radix Praeparata, Epimedium, Eucommia ulmoides, Rhizoma Drynariae, Angelica sinensis, Achyranthes, Astragalus propinquus, Psoralen, Cornus officinalis and licorice. A total of 87 drug pairs were obtained from the correlation analysis, and a total of 8 groups of potential core combination drugs and 4 potential new prescriptions were derived based on the cluster analysis. Subsequently, a network pharmacological analysis of the core drugs was conducted to obtain 173 active ingredients in the core drugs, including kaempferol, β-sitosterol, quercetin, etc. 298 targets of action, including MAPK3, STAT1, HSP90AA1, etc. 170 signaling pathways including AGE-RAGE, PI3 K/Akt, TNF, HIF-1 and others. The molecular docking results showed that 11 key active ingredients in the core drugs had stable binding to the target targets. This study showed that TCM treatment of PMOP is mainly based on “reinforcing liver and kidney, warmly invigorating spleen and stomach, activating blood and resolving stasis.” Core drugs therapy for PMOP is a comprehensive intervention through multi-component, multi-target, and multi-pathway approaches. The minimum binding energies between the 11 key active ingredients and the 11 key targets were calculated in a comprehensive analysis, which shows that the core drugs have good binding activities to their therapeutic targets, proving that the predictions of this study are reliable. In the future, it will provide certain medication basis and data support for TCM treatment of PMOP.

Synthesis, crystal structure, Hirshfeld surface, computational and biological studies of spiro-oxindole derivatives as MDM2-p53 inhibitors.

The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, 1H, 13C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC50 value of 8.13 ± 0.66µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.

An investigation on the cardioprotective potential of lichen compound protocetraric acid by H2O2-induced toxicity in H9c2 rat heart cells through in vitro and in silico analysis.

Worldwide, cardiovascular diseases (CVDs) are the leading cause of death and require treatment and prevention. Lichens are symbiotic organisms that are known to produce unique secondary metabolites and have been used as folk medicines. The aim of the study is to emphasize the importance of lichens in improving heart health, with the objective of investigating protocetraric acid, a lichen metabolite, for its antioxidant and cardioprotective potential by using in vitro and in silico techniques. Protocetraric acid (PRC) was isolated, characterized, and tested for antioxidant properties using six assays. In cardiovascular investigations, hydroxymethylglutaryl-coenzymeA reductase (HMGCR), angiotensin-converting enzyme inhibitory, and fibrinolytic capacities, along with enzyme inhibitory kinetics studies, were carried out. In silico toxicology and molecular docking analysis were done to determine the binding sites on target proteins. The cytoprotective ability of PRC was evaluated by H2O2-induced toxicity in H9c2 rat heart cells. Out of six lichens, the extract of F. caperata showed comparatively stronger antioxidant activity in terms of 1,1-diphenyl-2-picryl hydrazil (DPPH), scavenging of nitric oxide (SNO), and ferric reducing potential (FRAP) equivalent values. PRC showed significant antioxidant properties, and with respect to cardiovascular studies, PRC exhibited 86% HMGCR and 82% ACE inhibition, while 57% fibrinolysis at 320µM concentration. Inhibitory kinetic tests of PRC showed competitive and uncompetitive HMGCR and ACE inhibition types respectively. PRC showed minimum binding energies of - 7.9, - 8.9, and - 9.0kcal/mol with 1HWK, 1O8A, and 4BZS. The H9c2 cell line pre-treated with PRC was found to reduce H2O2 toxicity as well as increase cell viability. Protocetraric acid is a potent compound that has been experimentally shown to have hypocholesterolemic, hypotensive, and cardioprotective properties for treating cardiovascular diseases.

Unraveling the effective inhibition of α-terpinol and terpene-4-ol against Aspergillus carbonarius: Antifungal mechanism, ochratoxin A biosynthesis inhibition and degradation perspectives

Aspergillus carbonarius, a common food-contaminating fungus, produces ochratoxin A (OTA) and poses a risk to human health. This study aimed to assess the inhibitory activity of tea tree essential oil and its main components, Terpene-4-ol (T4), α-terpineol (αS), and 3-carene (3C) against A. carbonarius. The study showed αS and T4 were the main antifungal components of tea tree essential oil, which primarily inhibit A. carbonarius growth through cell membrane disruption, reducing antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase) and interrupting the tricarboxylic acid cycle. Furthermore, αS and T4 interacted with enzymes related to OTA biosynthesis. Molecular docking and molecular dynamics show that they bound mainly to P450 with a minimum binding energy of −7.232 kcal/mol, we infered that blocking the synthesis of OTA precursor OTβ. Our hypothesis was preliminarily verified by the detection of key substances in the OTA synthesis pathway. The results of UHPLC-QTOF-MS2 analysis demonstrated that T4 achieved a degradation rate of 43 % for OTA, while αS reached 29.6 %, resulting in final breakdown products such as OTα and phenylalanine. These results indicated that α-terpinol and Terpene-4-ol have the potential to be used as naturally safe and efficient preservatives or active packaging to prevent OTA contamination.

Binding and displacement study of gentamicin, 5-fluorouracil, oxytetracycline and rolitetracycline with (BSA: Drug2) complex using spectroscopic and calorimetric techniques: Biophysical approach

Understanding of energetics of interactions between drug and protein is essential in pharmacokinetics and pharmacodynamics study. The binding affinity (K) helps in investigating how tightly or loosely drug is bound to protein. The binding, displacement, conformational change and stability study of drugs- gentamicin (GM), 5-fluorouracil (5FU), oxytetracycline (OTC) and rolitetracycline (RTC) with bovine serum albumin (BSA) has been carried out in presence of each other drug by fluorescence, UV–visible spectroscopy, molecular docking, circular dichroism techniques and thermal denaturation method. The site marker study and docking methods have confirmed that 5FU and GM are able to bind at site 1 and OTC and RTC at site II of BSA. The order of their binding affinities with BSA for the binary system were as GM <5FU < OTC < RTC with the order of 102 < 103 < 105 < 105–6 M−1. The displacement study has shown that higher affinity drug decreases the equilibrium constant of another drug already in bound state with BSA if both these drugs are having the same binding site. Therefore 5FU, GM (binding site 1) drugs were not able to displace OTC and RTC (binding site 2) and vice-versa as they are binding at two different sites. The binding constant values were found to be decreasing with increasing temperature for all the systems involved which suggests static or mixed type of quenching, however can only confirmed with the help of TCSPC technique. The ΔG0 (binding energy) obtained from docking method were in accordance with the ITC method. From molecular docking we have determined the amino acid residues involved in binding process for binary and ternary systems by considering first rank minimum binding energy confirmation. From CD it has been observed that RTC causes most conformational change in secondary and tertiary structure of BSA due to the presence of pyrrole ring. OTC-RTC with higher affinity showed highest melting temperature Tm values while low affinity drugs in (5FU-GM) combination showed lowest Tm value. 5FU showed large endothermic denaturation enthalpy ΔHd0 due to the presence of highly electronegative fluorine atom in the pyridine analogue.

Adsorption behavior of Rh-VSe2 monolayer upon dissolved gases in transformer oil and the effect of applied electric field

Dissolved gas analysis (DGA) in transformer oil is an effective method to monitor the operating status of transformers. Based on fundamental principles, the adsorption behavior of decomposed gases from transformer oil (CO, CH4, C2H2, C2H4, and C2H6) on intrinsic and Rh-doped VSe2 monolayers is examined. The adsorption structure, adsorption energy, charge transfer, density of state, electron density difference, work function, and desorption properties are discussed to evaluate the potential applications of VSe2 monolayers as scavengers and gas-sensing materials for transformer oil decomposed gases. The results show that Rh dopant can be stably adsorbed on the surface of VSe2 monolayer, and the minimum binding energy is −4.957 eV. The adsorption behavior of oil-dissolved gases on the intrinsic VSe2 monolayer is weak. The sensing performance of VSe2 monolayer for oil-dissolved gas molecules is significantly enhanced after the introduction of Rh dopant. The sensing performance of Rh-VSe2 monolayer for CO, C2H2, C2H4 and C2H6 gases is stronger than that of CH4. Furthermore, in order to improve the applicability of the Rh doped VSe2 monolayer for the detection of oil-dissolved gases molecules. The effect of electric field on the sensing properties of gas molecules on Rh doped VSe2 monolayers is also investigated. Finally, the desorption performance of the system is evaluated based on the transition state theory and Van’t-Hoff-Arrhenius expression. The findings of the study not only disclose the method by which the Rh doped VSe2 monolayer detects the breakdown gasses in transformer oil, but they also offer theoretical recommendations for the advancement of VSe2-based sensors and scavengers.

PH-Dependent interactions between β-casein and blueberry anthocyanins based on typical thermal processing conditions: Stability, structural characterization, and binding mechanisms

The color and structural stability of blueberry anthocyanins (BAs) are significantly affected by pH changes during processing. In this study, we present the potential effects of the thermal stability, structural characterization, and binding mechanism of BAs with β-casein (β-CN) at pH 2, 4, and 6 for the first time. The pH was found significantly affect the ability of β-CN to protect BAs from thermal, vitamin C, and sucrose induced degradation. Scanning electron microscopy (SEM) resolved the microstructural differences of β-CN-BAs at varying pH values. Multispectral analysis showed that as pH increases, the electrostatic interaction between β-CN and the major monomer of anthocyanins Cyanidin-3-O-glucoside (C3G) are replaced by hydrogen bonding and van der Waals forces, and then electrostatic interactions are again the dominant force. In vitro gastrointestinal digestion confirmed that the protein stabilized C3G under varying pH conditions. Nuclear magnetic resonance (NMR) spectroscopy reveals the connection between the multiple equilibrium forms of C3G (hemiketal, cis-chalcone, and trans-chalcone) and β-CN on the formation of complexes between multiple equilibrium forms to specifically elucidate the mechanism of its stabilizing effect. Molecular docking simulation revealed the significance of electrostatic interaction and hydrogen bonding, where the highest binding match was achieved at pH 2, with a minimum binding energy. These interactions can effectively promote stable complexation of β-CN with C3G. These findings have practical implications for protein regulation of the relationship between the equilibrium forms of different anthocyanins and can guide the stabilization of anthocyanin-rich products.

Adsorption of Water on Vacancy Defective h-BN Bilayer at B and N Sites

&lt;&gt;Two dimensional (2D) materials are used to manufacture the various gadgets. Their properties are therefore appealing. In the present work, we have studied the structural, electronic, and magnetic properties of 2D bilayer hexagonal-Boron Nitride (h-BN), single B vacancy defect on h-BN (B-hBN), single N vacancy defect on h-BN (N-hBN), water adsorption; on B-hBN (w-B-hBN) and on N-hBN (w-N-hBN), materials by spin-polarized density functional theory (DFT) methods employing Quantum ESPRESSO (QE) computational tools. The structural stability of the h-BN, B-hBN, N-hBN, w-B-hBN, &amp; w-N-hBN materials has been investigated by determining their minimum ground state energy and binding energy, and found that they are stable materials. The pristine h-BN bilayer supercell structure is also found to be more compact than other defective configurations. By analyzing the band structures and density of states (DoS) plots of these materials, we have examined their electronic properties, and found that pristine h-BN has a broad bandgap, whereas B-hBN, N-hBN, w-B-hBN, &amp; w-N-hBN exhibit semiconducting nature. The DoS and partial density of states (PDoS) computations of the considered materials are used to study their magnetic properties. It is found that pristine h-BN is a non-magnetic, and B-hBN, N-hBN, w-B-hBN &amp; w-N-BN are magnetic materials. Therefore, vacancy defects on pristine h-BN, and water adsorption on vacancy defected h-BN materials cause it to change from non-magnetic to magnetic. They could find use in the domain of device applications.

In vitro antibacterial and antioxidant activity of flavonoids from the roots of Tephrosia vogelii: a combined experimental and computational study.

Tephrosia vogelii is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH2Cl2/MeOH (1:1) roots extract of T.vogelii afforded seven compounds namely; β-sitosterol (1a), stigmasterol (1b), 6a, 12a-dehydro-deguelin (2), tephrosin (3), maackiain (4), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6). GC-MS analysis of essential oils from the root of T.vogelii displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were themajor constituents. CH2Cl2/MeOH (1:1) extract, MeOH extract, maackiain (4) and obovatin (5) showed moderate inhibitory activity against Pseudomonas aeruginosa with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 μg/mL). 6a, 12a-dihydro-deguelin (2), and 6-oxo, 6a, 12a-dehydro-deguelin (6) displayed significant activity against S.epidermis with MIC values of 0.66 mg/mL. Tephrosin (3) and maackiain (4) also showed moderate antibacterial activity against Staphylococcus aureus and Proteus mirabilis with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 μg/mL). The radical scavenging activity results indicated that tephrosin (3), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6) showed potent DPPH scavenging activity with IC50 values of 10.97, 10.43 and 10.73 μg/mL, respectively, compared to ascorbic acid (IC50 of 5.83 μg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin (2) displayed the best binding energy of-8.1 kcal/mol towards pyruvate kinase of S.aureus (PDB ID: 3T07) and-7.9 kcal/mol towards P.mirabilis urease (PDB ID: 1E9Y) and DNA gyrase B of Escherichia coli (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to-8.0 kcal/mol). Maackiain (4) and obovatin (5) displayed the minimum binding energy of-7.9 and-8.2 kcal/mol towards the LasR protein of P.aeruginosa (PDB: ID 2UV) and S.epidermidis FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (2-6) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The invitro assessment results supported by the insilico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of T.vogelii.

ANTIBACTERIAL ACTIVITY OF AMPHIPHILES BASED ON INDOLYL-3-CARBOXYLIC ACIDS AND L-LYSINE WITH ETHYLENEDIAMINE LINKER

Recently, due to the growth of bacterial infections resistant to antibiotics, there is an urgent need to develop alternative antibacterial drugs. Alkyl-indolyl-L-lysine is a promising class of compounds; their amphiphilic structure is key in antimicrobial ef cacy. A scheme was developed and the synthesis of ve new derivatives of indolylbutyric and indolylacetic acids containing a polar amino acid residue with an ethylenediamine linker binding alkyl fragments of different lengths was carried out. The antibacterial activity of new amphiphiles against gram-positive and gram-negative bacterial strains was evaluated. The minimum binding energy of synthesized compounds with human serum albumin (HSA) was determined by the method of molecular docking. A lower af nity of the studied objects was shown compared to the control indolmycin.

Biological evaluation of levofloxacin and its thionated derivatives: antioxidant activity, aldehyde dehydrogenase enzyme inhibition, and cytotoxicity on A549 cell line.

Levofloxacin (LVX) is among the fluoroquinolones antibiotics that has also been studied in vitro and in vivo for its anticancer effects. In this study, we used LVX and novel LVX thionated derivatives; compounds 2 and 3, to evaluate their antioxidant activity, aldehyde dehydrogenase (ALDH) enzymes activity inhibition, and anticancer activity. Combination treatments with doxorubicin (DOX) were investigated as well. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the antioxidant activity. The NADH fluorescence spectrophotometric activity assay was used to determine the ALDH inhibitory effects. Resazurin dye method was applied for cell viability assays. Molecular Operating Environment software was used for the molecular docking experiments. Compared to ascorbic acid, DPPH assay showed that compound 3 had the highest antioxidant activity among the tested compounds with approximately 35% scavenging activity. On ALDH enzymes, compound 3 showed a significant ALDH activity inhibition compared to compound 2 at 200 µM. The IC50 values for the tested compounds were approximately 100 µM on A549 cell line, a non-small cell lung cancer (NSCLC) cell line. However, significant enhancement of cytotoxicity and reduction of IC50 values were observed by combining DOX and synergism was achieved with LVX with a combination index value of 0.4. The molecular docking test showed a minimum binding energy with a good affinity for compound 3 towards ALDH enzymes. Thionated LVX derivatives, may be repurposed for NSCLC therapy in combination with DOX, taking into account the antioxidant activity, ALDH activity inhibition, and the molecular docking results of compound 3.

New pyridine-based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities.

New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 μM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 μM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 μg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 μg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.

Exploratory studies on chrysin via antioxidant, antimicrobial, ADMET, PASS and molecular docking evaluations

IntroductionChrysin, a flavonoid found in Feng Jiao (Chinese name for propolis), exhibits a wide array of pharmacological activities and is recognized for the significant roles it plays in traditional Chinese medicine. The present study aimed to explore the in vitro antioxidant and antimicrobial potentials of chrysin and provide mechanistic insights via in silico experiments. MethodsThe in vitro antioxidant and antimicrobial activities of chrysin, a natural flavone found in propolis was investigated. Molecular docking interactions, the Adsorption, Distribution, Metabolism, Elimination and Toxicity (ADMET) and Prediction of Activity Spectra for Substances (PASS) were used to predict the biological activities of chrysin. ResultsChrysin exhibited a considerable 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging activity and ferric reducing antioxidant capacity. Chrysin demonstrated inhibition against S. typhi, and B. subtilis with lowest MIC value of 1.25 mg/mL which was similar to that of chloramphenicol. Drug-likeness and ADMET study of the two compounds showed their physicochemical properties as non-toxic, non-mutagenic, high permeability, good solubility and absorption characteristics. DiscussionThe research below shows that chrysin and silymarin had antioxidant, free radical scavenging, antibacterial, hepatoprotective and anticarcinogenic properties based on PASS prediction of biological activities. Molecular docking of chrysin and silymarin, a standard hepatoprotective drug, with tumour necrosis factor alpha converting enzyme (TACE) and manganese-dependent superoxide dismutase (SOD 2) showed interactions with LEU 401, VAL 402, HIS 405 amino acid residues at the active sites of TACE. Chrysin non-covalently interacted with amino acids of SOD 2 at the active site while silymarin non-covalently interacted at a site different from the active site. Silymarin demonstrated a minimum binding energy of – 9.7 Kcal/mol and – 7.0 Kcal/mol for TACE and SOD 2, respectively while chrysin showed a minimal binding energy of – 9.0 Kcal/mol and – 6.8 Kcal/mol for TACE and SOD2 respectively. ConclusionThe study concluded that chrysin exhibited antioxidant and antimicrobial activity via inhibition and regulation of TACE and SOD2 and possibly offer protection against hepatotoxicity in animal experimental models.

Analyzing Phytocompounds, Antioxidants, and In-Silico Molecular Docking of Plant-Derived Potential Andrographis paniculata Inhibitory Action to Managed Beta Thalassemia

It has long been known that medicinal plants are vital to human health and have been used for therapeutic purposes since the beginning of civilization. The goal of this study is to evaluate the scientific data supporting the use of the herbal remedy Andrographis paniculata in the management of beta thalassemia. Phytocompounds, one of the bases of traditional use, were assessed both qualitatively and quantitatively in five different extracts with varying solvent properties (methanol, chloroform, hexane, ethyl acetate, and aqueous), providing the fundamental explanation for the therapeutic relevance of this plant. The presence of flavonoids, phenols, tannins, saponins, and alkaloids in plant extracts was assessed. It was shown that ethanol extract had the highest concentration of phytocompounds among the various extracts, while chloroform extract had the lowest concentration. The plant's antioxidant activity was also assessed, and the results showed that the methanolic extract has potential antioxidant activity, as shown by the DPPH's lowest half-inhibitory concentration (IC50) values. To further evaluate the phytocompounds for their in-silico study, molecular docking techniques were employed. These phytocompounds (DL-alphatocopherol, 3,19-O-diacetylanhdroandrographolide, and 14-acetylandrographolide) to the fetal hemoglobin target protein PDBID:4MQJ were also found to have interactions with significantly minimum binding energies of −12.52 kcal/mol, −11.22 kcal/mol, and −11.08 kcal/mol, where DL-alphatocopherol was found to have the highest binding affinity (−12.524 kcal/mol) and interaction with the active site HIS97. The SwissADME was used to assess the drug-likeness and ADMET characteristics of phytocompounds derived from Andrographis paniculata. Based on chemical characteristics, drug-likeness score, and ADMET model, the present study selected and screened the phytocompounds DL-alphatocopherol, 3,19-O-diacetylanhdroandrographolide, and 14-acetylandrographolide, which are expected to have better drug-like features with improved toxicity profiles. Therefore, it makes sense to send the compounds reported in this work to an in-vivo analysis of therapeutic applicability due to their significant biological features.

Analyzing Phytocompounds, Antioxidants, and In-Silico Molecular Docking of Plant-Derived Potential Andrographis Paniculated Inhibitory Action to Managed Beta Thalassemia

It has long been known that medicinal plants are vital to human health and have been used for therapeutic purposes since the beginning of civilization. The goal of this study is to evaluate the scientific data supporting the use of the herbal remedy Andrographis paniculata in the management of beta thalassemia. Phytocompounds, one of the bases of traditional use, were assessed both qualitatively and quantitatively in five different extracts with varying solvent properties (methanol, chloroform, hexane, ethyl acetate, and aqueous), providing the fundamental explanation for the therapeutic relevance of this plant. The presence of flavonoids, phenols, tannins, saponins, and alkaloids in plant extracts was assessed. It was shown that ethanol extract had the highest concentration of phytocompounds among the various extracts, while chloroform extract had the lowest concentration. The plant's antioxidant activity was also assessed, and the results showed that the methanolic extract has potential antioxidant activity, as shown by the DPPH's lowest half-inhibitory concentration (IC50) values. To further evaluate the phytocompounds for their in-silico study, molecular docking techniques were employed. These phytocompounds (DL-alphatocopherol, 3,19-O-diacetylanhdroandrographolide, and 14-acetylandrographolide) to the fetal haemoglobin target protein PDBID:4MQJ were also found to have interactions with significantly minimum binding energies of -12.52 kcal/mol, -11.22 kcal/mol, and -11.08 kcal/mol, where DL-alphatocopherol was found to have the highest binding affinity (-12.524 kcal/mol) and interaction with the active site HIS97. The SwissADME was used to assess the drug-likeness and ADMET characteristics of phytocompounds derived from Andrographis panicluata. Based on chemical characteristics, drug-likeness score, and ADMET model, the present study selected and screened the phytocompounds DL-alphatocopherol, 3,19-O-diacetylanhdroandrographolide, and 14-acetylandrographolide, which are expected to have better drug-like features with improved toxicity profiles. Therefore, it makes sense to send the compounds reported in this work to an in vivo analysis of therapeutic applicability due to their significant biological features.