Integrated System Pharmacology Approaches to Elucidate Multi-Target Mechanism of Solanum surattense against Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors with high mortality. Chronic hepatitis B and C viruses, aflatoxins, and alcohol are among the most common causes of hepatocellular carcinoma. The limited reported data and multiple spectra of pathophysiological mechanisms of HCC make it a challenging task and a serious economic burden in health care management. Solanum surattense (S. surattense) is the herbal plant used in many regions of Asia to treat many disorders including various types of cancer. Previous in vitro studies revealed the medicinal importance of S. surattense against hepatocellular carcinoma. However, the exact molecular mechanism of S. surattense against HCC still remains unclear. In vitro and in silico experiments were performed to find the molecular mechanism of S. surattense against HCC. In this study, the network pharmacology approach was used, through which multi-targeted mechanisms of S. surattense were explored against HCC. Active ingredients and potential targets of S. surattense found in HCC were figured out. Furthermore, the molecular docking technique was employed for the validation of the successful activity of bioactive constituents against potential genes of HCC. The present study investigated the active “constituent–target–pathway” networks and determined the tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mammalian target of rapamycin (mTOR), Bcl-2-like protein 1(BCL2L1), estrogen receptor (ER), GTPase HRas, hypoxia-inducible factor 1-alpha (HIF1-α), Harvey Rat sarcoma virus, also known as transforming protein p21 (HRAS), and AKT Serine/Threonine Kinase 1 (AKT1), and found that the genes were influenced by active ingredients of S. surattense. In vitro analysis was also performed to check the anti-cancerous activity of S. surattense on human liver cells. The result showed that S. surattense appeared to act on HCC via modulating different molecular functions, many biological processes, and potential targets implicated in 11 different pathways. Furthermore, molecular docking was employed to validate the successful activity of the active compounds against potential targets. The results showed that quercetin was successfully docked to inhibit the potential targets of HCC. This study indicates that active constituents of S. surattense and their therapeutic targets are responsible for their pharmacological activities and possible molecular mechanisms for treating HCC. Lastly, it is concluded that active compounds of S. surattense act on potential genes along with their influencing pathways to give a network analysis in system pharmacology, which has a vital role in the development and utilization of drugs. The current study lays a framework for further experimental research and widens the clinical usage of S. surattense.     

Optimized Green Extraction of Polyphenols from Cassia javanica L. Petals for Their Application in Sunflower Oil: Anticancer and Antioxidant Properties

The total phenolic content (TPC) from Cassia javanica L. petals were extracted using ethanolic solvent extraction at concentrations ranging from 0 to 90% and an SCF-CO₂ co-solvent at various pressures. Ultrasound-assisted extraction parameters were optimized using response surface methodology (RSM). Antioxidant and anticancer properties of total phenols were assessed. An SCF-CO₂ co-solvent extract was nano-encapsulated and applied to sunflower oil without the addition of an antioxidant. The results indicated that the best treatment for retaining TPC and total flavonoids content (TFC) was SCF-CO₂ co-solvent followed by the ultrasound and ethanolic extraction procedures. Additionally, the best antioxidant activity by β-carotene/linoleic acid and DPPH free radical-scavenging test systems was observed by SCF-CO₂ co-solvent then ultrasound and ethanolic extraction methods. SCF-CO₂ co-solvent recorded the highest inhibition % for PC3 (76.20%) and MCF7 (98.70%) and the lowest IC₅₀ value for PC3 (145 µ/mL) and MCF7 (96 µ/mL). It was discovered that fortifying sunflower oil with SCF-CO₂ co-solvent nanoparticles had a beneficial effect on free fatty acids and peroxide levels. The SCF-CO₂ method was finally found to be superior and could be used in large-scale processing.     

Radiosynthesis and Biodistribution of <Superscript>99m</Superscript>Tc-Metronidazole as an <Emphasis Type="Italic">Escherichia coli</Emphasis> Infection Imaging Radiopharmaceutical

Bacterial infection poses life-threatening challenge to humanity and stimulates to the researchers for developing better diagnostic and therapeutic agents complying with existing theranostic techniques. Nuclear medicine technique helps to visualize hard-to-diagnose deep-seated bacterial infections using radionuclide-labeled tracer agents. Metronidazole is an antiprotozoal antibiotic that serves as a preeminent anaerobic chemotherapeutic agent. The aim of this study was to develop technetium-99m-labeled metronidazole radiotracer for the detection of deep-seated bacterial infections. Radiosynthesis of ^99mTc-metronidazole was carried by reacting reduced technetium-99m and metronidazole at neutral pH for 30 min. The stannous chloride dihydrate was used as the reducing agent. At optimum radiolabeling conditions, ~ 94% radiochemical was obtained. Quality control analysis was carried out with a chromatographic paper and instant thin-layer chromatographic analysis. The biodistribution study of radiochemical was performed using Escherichia coli bacterial infection-induced rat model. The scintigraphic study was performed using E. coli bacterial infection-induced rabbit model. The results showed promising accumulation at the site of infection and its rapid clearance from the body. The tracer showed target-to-non-target ratio 5.57 ± 0.04 at 1 h post-injection. The results showed that ^99mTc-MNZ has promising potential to accumulate at E. coli bacterial infection that can be used for E. coli infection imaging.     

Characterisation of some exotic fruits (Morus nigra, Morus alba, Salvadora persica and Carissa opaca) used as herbal medicines by neutron activation analysis and estimation of their nutritional value

In the under developed countries, the people of far-flung rural areas still depend to a large extent upon herbal medicines. At the foundation of usage of herbal medicine is the experience of thousands of years. The present paper deals with the characterisation of exotic fruits for essential and toxic elements. The samples include Morus nigra, Morus alba, Salvadora persica and Carissa opaca (from low and high altitude). Two standardizations of neutron activation analysis, that is, semi-absolute k ₀-instrumental neutron activation analysis (k ₀-INAA) and epithermal neutron activation analysis (ENAA) were employed for the quantification of elements. The analysis methodologies were validated by analyzing the IAEA-336 (lichen) and NIST-SRM-1572 (citrus leaves). Sixteen elements including Br, Ca, Cl, Co, Cr, Fe, I, K, Mg, Mn, Na, Rb, Sb, Sc Sr, and Zn were determined in all samples. Daily intakes of various elements from the samples were measured and compared with the dietary reference intakes. Additionally, principal component analysis was performed to extract information regarding samples and elements.     

Highly selective enrichment of phosphopeptides using poly(dibenzo‐18‐crown‐6) as a solid‐phase extraction material

A poly(dibenzo‐18‐crown‐6) was used as a new solid‐phase extraction material for the selective enrichment of phosphopeptides. Isolation of phosphopeptides was achieved based on specific ionic interactions between poly(dibenzo‐18‐crown‐6) and the phosphate group of phosphopeptides. Thus, a method was developed and optimized, including loading, washing and elution steps, for the selective enrichment of phosphopeptides. To assess this potential, tryptic digest of three proteins (α‐ casein, β‐casein and ovalbumin) was applied on poly(dibenzo‐18‐crown‐6). The nonspecific products were removed by centrifugation and washing. The spectrometric analysis was performed using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Highly selective enrichment of both mono‐ and multiphosphorylated peptides was achieved using poly(dibenzo‐18‐crown‐6) as solid‐phase extraction material with minimum interference from nonspecific compounds. Furthermore, evaluation of the efficiency of the poly(dibenzo‐18‐crown‐6) was performed by applying the digest of egg white. Finally, quantum mechanical calculations were performed to calculate the binding energies to predict the affinity between poly(dibenzo‐18‐crown‐6) and various ligands. The newly identified solid‐phase extraction material was found to be a highly efficient tool for phosphopeptide recovery from tryptic digest of proteins.     

Unprecedented isolation of a dinuclear tin (II) complex stabilized by pyridine‐2,6‐dimethanol: structure,DFT and in vitro screening of cytotoxic properties

In this work, we report a novel dinuclear Sn (II) complex, [Sn₂(Hpdm)₂(H₂O)₆] 2H₂O 2Cl ( 1 ) (H₂pdm = pyridine‐2,6‐dimethanol), which has been crystallized out and characterized by elemental analysis, FTIR, ¹H and ¹³C NMR, single crystal X‐ray studies and Density Functional Theory (DFT) analysis. X‐ray structure of 1 has confirmed it to be a dinuclear alkoxo‐bridged Sn (II) species where each metal adopts a seven coordinate distorted pentagonal bipyramidal (pbp) geometry. This is the first hepta‐coordinated Sn (II) complex ever isolated apart from already reported stannylenes. Spin density plots from DFT support the +2 oxidation state of each tin metal. Hirshfeld surface analysis reveals the presence of various H‐bonding interactions in the molecule and molecular docking results along with DFT confirm higher binding affinity of the present complex towards DNA. Moreover, the complex exhibits promising anticancer activities against HeLa and A549 cancer cell lines.     

Synthesis, Crystal Structure and ab initio Studies of Cyclohexyl N-Phenylcarbamate

Abstract  

Cyclohexyl N-phenylcarbamate, C₁₃H₁₇NO₂ (I), which is a useful target for biotransformations by fungi, has been synthesized and the structure has been solved by X-ray diffraction. The crystals are triclinic, space group P [`1] \bar{1} , with a = 5.2581 (2) ?, b = 9.5080 (3) ?, c = 12.6165 (4) ?, α = 70.544 (2)°, β = 89.075 (2)°, γ = 80.447 (2)°, M _r = 219.28, V = 585.96 (3) ?³, Z = 2 and R = 0.065. In the title compound the phenyl ring makes a dihedral angle of 30.68(7)° with the carbamate group The molecules are linked into infinite chains via N–H···O hydrogen bonds along the a axis. These hydrogen-bonded chains are further linked by weaker C–H···π interactions. Quantum-mechanical ab initio calculations for the free molecule reproduce well the observed bond lengths and valency angles but show that the crystal packing might be responsible for the rotation of the phenyl ring out of the carbamate plane in the solid state conformation.     

Synthetic ion channels and pores (2004-2005)

This critical review covers synthetic ion channels and pores created between January 2004 and December 2005 comprehensively. The discussion of a rich collection of structural motifs may particularly appeal to organic, biological, supramolecular and polymer chemists. Functions addressed include ion selectivity and molecular recognition, as well as responsiveness to light, heat, voltage and membrane composition. The practical applications involved concern certain topics in medicinal chemistry (antibiotics, drug delivery), catalysis and sensing. An introduction to principles and methods is provided for the non-specialist; some new sources of inspiration from fields beyond chemistry are highlighted.     

Development and application of spectrophotometric methods for the determination of citalopram hydrobromide in dosage forms

Study was carried out to develop two simple, fast, accurate and sensitive spectrophotometric methods (A and B) for the determination of citalopram hydrobromide in commercial tablet formulations. In method A, UV spectrophotometer determined the contents of citalopram hydrobromide in tablets at 240 nm in methanol solvent. The linear range was 5-40 microg ml-1 with molar absorptivity 1.4x10(4) l mol-1 cm-1. While the method B based on the reaction of citalopram base as n-electron donor with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as pi-acceptors to give highly colored complex species that absorb maximally at 590 nm. Beer's law was obeyed in the concentration limit of 10-250 microg ml-1 with molar absorptivity 3.3x10(3) l mol-1 cm-1 for citalopram hydrobromide. The limits of detection and limit of quantification was calculated and found to be 5.2 microg ml-1 and 17.4 microg ml-1 respectively. The proposed methods were found to be rapid, accurate, precise and sensitive for the determination of citalopram hydrobromide in commercial tablet formulations with out interferences from common additives encountered.