Exploring Cassia mimosoïdes as a promising natural source of steroids with potent anti-cancer, urease inhibition, and antimicrobial properties.

The genus Cassia is a rich source of physiologically active secondary metabolites, including a novel compound named 21-methylene-24-ethylidene lophenol, alongside 15 known compounds. These compounds were characterized using different spectroscopic techniques. They exhibited promising antimicrobial activity, particularly against bacteria causing gastrointestinal infections. Compound 1 showed strong anti-bacterial activity against H. pylori and S. aur with MIC values of 0.28 and 0.12 µg mL-1 respectively. The study investigated their impact on H. pylori, a contributor to ulcer development, by inhibiting the urease enzyme. Inhibiting urease can reduce H. pylori's pathogenic potential, evident from the fact that the compounds evaluated toward urease enzyme showed higher inhibitory activity (1.024 ± 0.43 6.678±0.11 µM) compared to standard thiourea (IC50 = 18.61 ± 0.11 µM). Molecular docking studies confirmed their inhibitory action, with compound 7 notably outperforming thiourea in inhibiting urease (-6.95 kcal mol-1vs. -3.13 kcal mol-1). Additionally, these compounds showed positive effects on liver functioning, which H. pylori can impair. Compound 9 shows the best response against human HepG2 liver cancer cell lines i.e., % viability is 14.47% ± 0.69 and IC50 is 7.8 µM ± 0.21. These compounds hold potential as lead compounds for addressing gastrointestinal and liver disorders caused by H. pylori.

Visible Light-Induced Reactive Yellow 145 Discoloration: Structural and Photocatalytic Studies of Graphene Quantum Dot-Incorporated TiO2.

Visible light-induced photocatalytic treatment of organic waste is considered a green and efficient route. This study explored the structural and photocatalytic performance of graphene quantum dot (GQD)-incorporated TiO2 nanocomposites to treat reactive yellow 145 (RY145) dye. For the effective removal of the RY145, efforts were made to better understand the kinetics of the process and optimization of the treatment parameters. Different GQD-doped TiO2 nanocomposites were synthesized employing the sol-gel method. Physicochemical characteristics of the synthesized nanocomposites were studied through FTIR, XRD, UV-visible spectroscopy, SEM, and EDX. Screening studies were conducted for synthesis and reaction optimization. The results indicated that GQD-TiO2 significantly enhanced the photocatalytic discoloration for RY145 dye. Among the synthesized nanocomposites, 15GQD-TiO2 calcined at 300 exhibited 99.3% RY145 discoloration in 30 min under visible light irradiation. Following the pseudo-first-order reaction, the photocatalytic reaction constant K app progressively declined with an increase in the concentration of RY145. The heterogeneous reaction system conformed to the Langmuir-Hinshelwood isotherm, as indicated by the K C (1.08 mg L-1 min-1) and the K LH (0.18 L mg-1) values. O2 •- was found to be the major contributor in GQD-TiO2-300 to decolorize RY154, while TiO2 and GQDs played a vital role in generation of electrons and holes. Additionally, after recycling to the seventh cycle, only 9% decline in photocatalytic performance was observed for the synthesized nanocomposite.

Unraveling the possible inhibitors for Chorismate synthase to combat tuberculosis using in silico approach.

Tuberculosis antibiotic resistance is a huge concern to the global population. The goal of this study was to find new and effective compounds to treat multidrug-resistant tuberculosis by targeting Chorismate synthase (CS), a crucial enzyme for Mycobacterium tuberculosis survival (MbT). The potential of a library of compounds as selective anti - tuberculosis drugs was investigated. Docking was first conducted using MoE to determine the effectiveness of the compounds. Molecular docking studies followed by MD simulation studies (total of 500 ns) in combination with free energy calculations grade the ligands in terms of their binding affinities. In the ligand bound state of the CS, MD simulations revealed a change from stretched to bended motional shift in loop L19. The RMSF analysis also revealed this flexibility, which was confirmed by visual inspection of L19 at various time intervals during the experiment. It appears that ZF1(-25.43Kcal/mol) and ZF2 (-22.04Kcal/mol) form hbonds and have a high binding energy in the active region of protein. Residues wise distribution of binding energy reveals that Arg144, Trp4, Thr6, and L19 amino acid residues are engaged in binding of CS with inhibitors. In summary, the findings suggest that compounds ZF1 and ZF2 may be more effective and selective anti-TB agents than currently available drugs. Also the role of L19, mediated by αH9 and αH5 in the retention of ligand inside the active pocket, through the formation of lid was also revealed. This knowledge will aid in the discovery of drugs that are potent CS inhibitors. More experimental research and a better understanding of the structure-activity relationship could aid in the development of possible candidates with better CS inhibition.Communicated by Ramaswamy H. Sarma.

Comparative efficacy of cephradine-loaded silver and gold nanoparticles against resistant human pathogens.

Infections caused by drug-resistant bacteria are major health concerns worldwide. We successfully synthesized cephradine gold nanoparticles (Ceph-Au NPs) and cephradine silver nanoparticles (Ceph-Ag NPs) and compared their efficacy against resistant human pathogens. X-Ray diffraction (XRD), Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) results showed that average particle size of Ceph-Au NPs and Ceph-Ag NPs were 7 and 12 nm, respectively. Fourier Transform Infra-red spectroscopy (FTIR) spectra revealed the conjugation of -NH2 and -OH functional moieties with the nanoparticle (NP) surfaces. These NPs significantly inhibited the biofilm of Streptococcus mutans (S. mutans) and methicillin-resistant Staphylococcus aureus (MRSA) in the range of 61.25-250 µg/mL. Ceph-Au NPs are more active than Ceph-Ag NPs and can be used to treat the diseases associated with MRSA and S. mutans.

Isoxazole Derivatives against Carbonic Anhydrase: Synthesis, Molecular Docking, MD Simulations, and Free Energy Calculations Coupled with In Vitro Studies.

Heterocyclic compounds with a five-membered ring as a core, particularly those containing more than one heteroatom, have a wide spectrum of biological functions, especially in enzyme inhibition. In this study, we present the synthesis of five-membered heterocyclic isoxazole derivatives via sonication of ethyl butyrylacetate with aromatic aldehyde in the presence of a SnII-Mont K10 catalyst. The synthesized compounds were characterized using sophisticated spectroscopic methods. In vitro testing of the compounds reveals three derivatives with significant inhibitory action against carbonic anhydrase (CA) enzyme. The compound AC2 revealed the most promising inhibitory activity against CA among the entire series, with an IC50 = 112.3 ± 1.6 µM (%inh = 79.5) followed by AC3 with an IC50 = 228.4 ± 2.3 µM (%inh = 68.7) compared to the standard with 18.6 ± 0.5 µM (%inh = 87.0). Molecular docking (MD) study coupled with extensive MD simulations (400 ns) and MMPBSA study fully supported the in vitro enzyme inhibition results, evident from the computed ΔG bind (AC2 = -13.53 and AC3 = -12.49 kcal/mol). The in vitro and in silico studies are also augmented by a fluorescence-based enzymatic assay in which compounds AC2 and AC3 showed significant fluorescence enhancement. Therefore, on the basis of the present study, it is inferred that AC2 and AC3 may serve as a new framework for designing effective CA inhibitors.

Synthesis of gemifloxacin conjugated silver nanoparticles, their amplified bacterial efficacy against human pathogen and their morphological study via TEM analysis.

Drug-loaded nanoparticles (NPs) allow specific accumulation and controlled release of drugs to infected tissues with minimal cytotoxicity. In this study, gemifloxacin conjugated silver nanoparticles (Gemi-AgNPs) were synthesized, and the amplification of their antibacterial potential against the human pathogen as well as their stability was monitored under physiological conditions. Fourier transform infrared spectroscopy (FTIR) analysis demonstrated the interaction between -NH2 and -OH functional moiety and the metal surface. The morphological analyses via transmission electron microscopy revealed that Gemi-AgNPs has a round oval shape and average particle size of 22.23 ± 2 nm. The antibacterial and antibiofilm activities of these NPS showed that Gemi-AgNPs exhibit excellent antimicrobial and biofilm inhibition activity against human pathogens, namely, Proteus mirabilis (P. mirabilis) and methicillin-resistant Staphylococcus aureus (MRSA). A significant increase in the antibiofilm activity of Gemi-AgNPs was confirmed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining, and microscopic analysis. Gemi-AgNPs exhibited the ability to inhibit urease with an IC50 value of 57.4 ± 0.72 µg/mL. The changes in the bacterial cell morphology were analyzed via TEM, which revealed that cell membranes disrupted and completely destroyed the cell morphology by the treatment of Gemi-AgNPs.

Pharmacophore model-based virtual screening, docking, biological evaluation and molecular dynamics simulations for inhibitors discovery against α-tryptophan synthase from Mycobacterium tuberculosis.

Discovery of new anti-tuberculosis drugs with novel mode of action is urgently needed. The tryptophan synthase is a genetically validated enzyme that catalyzes last step of tryptophan biosynthetic pathway required for growth and survival of Mycobacterium tuberculosis. Here, a ligand-based pharmacophore model was built using molecular operating environment (MOE) software (version 2010.12) and validation of generated pharmacophoric features was done using active, inactive and decoy set of molecules. The generated pharmacophore model was used for screening of 7,523,972 drug-like molecules of ZINC database. The best matches (RMSD < 1) retrieved as a result of screening were subjected to molecular docking studies into active pocket of α-subunit of tryptophan synthase from M. tuberculosis. The five hits were selected and validated through anti-tuberculosis activity analysis. Finally, a new inhibitor ZINC09150898 has been identified with best binding score -32.07 kcal/mol, showing 100% growth inhibition of M. tuberculosis (H37Rv strain) at 50 µg/mL. This identified inhibitor-protein complex was further subjected to MD simulations studies (50 ns) involving root mean square deviation, root mean square fluctuation, secondary structure analysis and pocket interaction analysis to explore its binding mode stability inside active pocket. The binding free energies of inhibitor-protein complex through MM-PBSA analysis suggested that van der Waals interactions play a vital role for retention of identified inhibitor inside the protein pocket. All these analyses confirmed retention of ligand inside pocket and no unfolding in protein structure was observed over explored time scale.Communicated by Ramaswamy H. Sarma.

Three new acrylic acid derivatives from Achillea mellifolium as potential thymidine phosphorylase inhibitor: molecular docking and MD simulation studies.

Discovery of potent inhibitors of thymidine phosphorylase (TP) can offer appropriate approach in cancer treatment owing to it's over expression in various human tumors compared to normal healthy tissues. Thymidine phosphorylase alongside 2-deoxy-D-ribose are reported as promoters of unwanted angiogenesis in cancerous cells. In this study, three new acrylic acid derivatives (1-3) have been isolated from ethyl acetate fraction of Achillea mellifolium. The characterization of these compounds (1-3) was done using UV, IR, 1 D and 2 D-NMR spectroscopy (1H-NMR, 13C-NMR, HMBC, NOESY) and mass spectrometry. The structure of these acrylic acid derivatives were ethyl (E)-3-((1S,5R)-5-methoxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)acrylate (1), methyl (E)-3-((1S,5R)-5-methoxy-2,6,6-trimethyl-4-oxocyclohex-2-en-1-yl)acrylate (2) and (4S,6R)-6-methoxy-3,5,5-trimethyl-4-((E)-3-oxobut-1-en-1-yl)cyclohex-2-en-1-one (3). Thymidine phosphorylase (TP) inhibition studies showed compound 3 as most active inhibitor of TP with IC50 value 57.81 ± 3.41 while compound 1 and 2 showed IC50 value as 158.9 ± 0.97 and 89.92 ± 0.37, respectively. In addition, molecular docking studies of compound (1-3) were performed to shed light on their binding interaction patterns for binding into active pocket of TP. Similarly, all compounds (1-3) were evaluated for their anti-oxidant potential showing anti-oxidant activities with IC50 value ranging from 49.73 ± 0.41 to 79.81 ± 0.39. Later, these compound-protein (1-3) complexes were further subjected to MD simulations studies (50 ns) involving root mean square deviation, root mean square fluctuation, and secondary structure analysis to explore their binding mode stability inside active pocket. Communicated by Ramaswamy H. Sarma.

Recent advances in combinatorial cancer therapy via multifunctionalized gold nanoparticles.

The diverse behavior of nanogold in the therapeutic field is related to its unique size and shape. Nanogold offers improvements in modern diagnostic and therapeutic implications, increases disease specificity and targeted drug delivery, and is relatively economical compared with other chemotherapeutic protocols. The diagnosis of cancer and photothermal therapy improve drastically with the implementation of nanotechnology. Different types of nanoparticles, that is, gold silica nanoshells, nanorods and nanospheres of diverse shapes and geometries, are used widely in the photothermal therapy of cancerous cells and nodules. Numerous reviews have been published on the therapeutic applications of gold nanoparticles, but studies on combinatorial applications of nanogold in cancer therapy are limited. This review focuses on the combinatorial cancer therapy using optical properties of nanogold with different shapes and geometries, and their therapeutic applications in cancer diagnosis, photothermal therapy, cancer imaging and targeted drug delivery.

Photocatalytic degradation and kinetic modeling of azo dye using bimetallic photocatalysts: effect of synthesis and operational parameters.

Industrial wastewaters are the major source polluting the surface and ground water resources. Pollutants released along with the untreated textile industry wastewaters are responsible for the great damage to the natural resources like water. Considering the hazardous effects of the azo dyes (textile coloring agents) and their byproducts, there is a need to develop cost-effective and efficient treatment method for the textile wastewaters as such dyes have been reported as toxic, mutagenic, and carcinogenic and can cause direct demolition of aquatic communities. One of the possible and effective treatment methods is the use of TiO2 photocatalysis due to its chemical stability, low cost, and non-toxic nature. The present study explored the photocatalytic potential of anatase-type of bimetallic Cu-Ni/TiO2 photocatalysts under visible light irradiation for possible photocatalytic degradation and mineralization of Methyl Orange (MO), as model azo dye. The focus was to correlate the synthesis (different calcination temperatures, phase composition of TiO2 either anatase or rutile, and metal ion loading in terms of concentration and composition (Cu:Ni)) and operational parameters (photocatalyst loading, pollutant concentration, and irradiation time) that were believed responsible for the enhanced photocatalytic performance. Blank experiments were carried out to check the effect of metal loading in comparison to bare TiO2 and effect of absence or presence of light and photocatalysts on MO photodegradation. Results obtained using bimetallic photocatalysts are promising as compared to bare TiO2 as 100% MO removal and ~ 90% %COD removal were obtained in 90 min of irradiation, obeying a pseudo-first-order kinetics with photocatalytic reaction via the Langmuir-Hinshelwood mechanism with a good linear fit. Photocatalysts synthesized using anatase TiO2 were reported with improved performance compared to rutile phase. It is evident that synthesis parameters influence photocatalyst performance directly. The higher rate constant (> 1) that proves the excellent adsorption capacity of the tested photocatalysts for tested pollutants on the surface may have a great prospective for photocatalytic water purification at neutral pH.

Loading AKBA on surface of silver nanoparticles to improve their sedative-hypnotic and anti-inflammatory efficacies.

Aim: Acetyl-11-keto-ß-boswellic acid (AKBA) is a potent anti-inflammatory compound limited by its low water solubility and bioavailability. To load AKBA on silver nanoparticles (AgNPs) to improve bioavailability and water solubility of the compound. Materials & methods: AKBA-AgNPs were chemically synthesized and characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. AKBA and AKBA-Ag were studied for their sedative-hypnotic and anti-inflammatory efficacies. Results: Pretreatment with AKBA or AKBA-Ag caused significant dose-dependent sedative-hypnotic effects at 5 and 10 mg/kg intraperitoneal. The effects of AKBA-loaded AgNPs caused pronounced changes in mice compared with those of AKBA, and the AKBA-AgNPs demonstrated anti-inflammatory effects that were superior to those of AKBA. Conclusion: The loading of AKBA on nanoparticles improved its pharmacokinetic effects, and capacity for drug delivery.

Physiological response of spinach to toxic heavy metal stress.

This study was carried out to investigate the concentration of two heavy metals, i.e., mercury (Hg) and arsenic (As) in soil and plant. Spinach (Spinacia oleracea L.) was used as a test vegetable in a pot experiment. Five spiked concentrations of both the metals along with sewage water were used as treatments. The analyses of the metals were determined in two cuttings. The results showed significant effect of treatments on the concentration of the two metals in soil and plant. The concentrations of As recorded were higher in 1st spinach cutting and reduced in the second harvest. However, comparing the two metal concentrations, it was found that As was absorbed greater as compared with Hg. Analyzing the plant growth parameter, it was found that metal stress has significantly influenced the plant growth. In sewage water pots, As was significantly higher than Hg. The transfer factor from soil to plant showed higher As in plants at lower concentration, but at higher As levels, the transfer rate declined, while Hg showed it was completely inverse. Positive correlation was found between soil applied metal concentration and plant uptake. It may be concluded from the above results that spinach is a good accumulator of heavy metals and has shown significant result of both As and Hg accumulation in plant. The concentration increased with the increasing concentration in soil.

Rifampicin conjugated silver nanoparticles: a new arena for development of antibiofilm potential against methicillin resistant Staphylococcus aureus and Klebsiella pneumoniae.

Background: Infections caused by drug resistant bacteria are a major health concern worldwide and have prompted scientists to carry out efforts to overcome this challenge. Researchers and pharmaceutical companies are trying to develop new kinds of antimicrobial agents by using different physical and chemical methods to overcome these problems. Materials and methods: In the present study, rifampicin conjugated silver (Rif-Ag) nanoparticles have successfully been synthesized using a chemical method. Characterization of the nanoparticles was performed using a UV-Vis spectrophotometer, FTIR, SEM, TEM, and AFM. Results: The AFM, SEM, and TEM results showed that the average particle size of Rif-Ag nanoparticles was about 15-18±4 nm. The FTIR spectra revealed the conjugation of -NH2 and -OH functional moiety with silver nanoparticles surface. Considering the penetrating power of rifampicin, the free drug is compared with synthesized nanoparticle for antimicrobial, biofilm inhibition, and eradication potential. Synthesized nanoparticles were found to be significantly active as compared to drug alone. Conclusion: This study has shown greater biofilm inhibitory and eradicating potential against methicillin resistant Staphylococcus aureus and Klebsiella pneumoniae, as evident by crystal violet, MTT staining, and microscopic analysis. So, it will be further modified, and studies for the mechanism of action are needed.

Apoptotic and antimetastatic activities of betulin isolated from Quercus incana against non-small cell lung cancer cells.

BACKGROUND: Globally, the prevalence and mortality rates of lung cancer have been escalated with the increasing trend of tobacco smoking. The toxicity and irresponsive nature of the available drugs for lung cancer treatment demands an alternative approach. METHODS: In this study, four known compounds namely, cirsimaritin (4',5, -dihydroxy-6,7-di-methoxyflavone) (1), eupatorin (5,3'-dihydroxy-6,7,4'-trimethoxyflavone) (2), betulin (Lup-20 (29)-ene-3, 28-diol) (3), and ß-amyrin acetate (12-Oleanen-3yl acetate) (4) have been isolated from the leaves extract of Quercus incana. Preliminary screening of these natural compounds (1-4) was performed against non-small cell lung carcinoma (NCI-H460) and normal mouse fibroblast (NIH-3T3) cell lines. RESULTS: The compounds were found to be antiproliferative against cancer cells with wide therapeutic index in comparison to the normal cells. Effects of betulin (3) on cell migration, invasion, apoptosis, and expression of important apoptosis- and metastasis-related markers were observed at different concentrations. The results showed significant dose-dependent induction of apoptosis after the treatment with betulin (3) followed by increased expression of the caspases family (ie, caspase-3, -6, and -9), proapoptotic genes (BAX and BAK), and inhibiting anti-apoptotic genes (BCL-2L1 and p53). Furthermore, wound healing and transwell invasion assays suggested that betulin (3) could also regulate metastasis by inhibiting MMP-2/-9. Osteopontin, a central regulator of apoptosis and metastasis was also inhibited in a dose-dependent manner. CONCLUSION: The present findings suggest that betulin (3) can be an attractive chemotherapeutic target for treating resistant lung cancers.

Identification of new benzamide inhibitor against α-subunit of tryptophan synthase from Mycobacterium tuberculosis through structure-based virtual screening, anti-tuberculosis activity and molecular dynamics simulations.

Multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure-based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the α-subunit of tryptophan synthase (α-TRPS) from Mycobacterium tuberculosis essential for bacterial survival. Based on physiochemical properties analysis and molecular docking, the seven candidate compounds were selected and evaluated through whole cell-based activity against the H37Rv strain of M. tuberculosis. A new Benzamide inhibitor against α-subunit of tryptophan synthase (α-TRPS) from M. tuberculosis has been identified causing 100% growth inhibition at 25 µg/ml and visible bactericidal activity at 6 µg/ml. This benzamide inhibitor displayed a good predicted binding score (-48.24 kcal/mol) with the α-TRPS binding pocket and has logP value (2.95) comparable to Rifampicin. Further refinement of docking results and evaluation of inhibitor-protein complex stability were investigated through Molecular dynamic (MD) simulations studies. Following MD simulations, Root mean square deviation, Root mean square fluctuation and secondary structure analysis confirmed that protein did not unfold and ligand stayed inside the active pocket of protein during the explored time scale. This identified benzamide inhibitor against the α-subunit of TRPS from M. tuberculosis could be considered as candidate for drug discovery against TB and will be further evaluated for enzyme-based inhibition in future studies.

Isolation and Characterization of Two New Secondary Metabolites From Quercus incana and Their Antidepressant- and Anxiolytic-Like Potential.

The ethyl acetate fraction of Quercus incana yielded two new compounds [1 and 2]. The characterization and structure elucidation of these compounds were carried out through various spectroscopic techniques such as mass spectrometry along with one- and two-dimensional NMR techniques. The structural formula was deduced to be 2-(4-hydroxybutan-2-yl)-5-methoxyphenol [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. The elevated plus maze (EPM) and light-dark box (LDB) tests (classical mouse models) were performed in order to reveal the anxiolytic potential of both compounds [1 and 2]. Both compounds displayed dose-dependent increases in open-arm entries and time spent in open arms in EPM (∗P < 0.05, ∗∗P < 0.01), and increased the time spent in the lit compartment and increased transitions between the two compartments in LDB test (∗P < 0.05, ∗∗P < 0.01). Co-administration of selective benzodiazepine (BZP) receptor antagonist, flumazenil (2.5 mg/kg) with compounds [1 and 2] decreased the anxiolytic-like activity of both compounds in the EPM indicating BZP-binding site of GABA-A receptors are involved in the anxiolytic-like effect. Similarly, both compounds at the dose level of 10 and 30 mg/kg, i.p. exerted pronounced antidepressant-like effect in both forced swimming as well as tail suspension tests (∗P < 0.05, ∗∗P < 0.01; ANOVA followed by Dunnett's post hoc test). The effect at 30 mg/kg was comparable to the reference drug imipramine (60 mg/kg).

Isolation and Characterization of Two New Antimicrobial Acids from Quercus incana (Bluejack Oak).

Two new compounds [1-2] were purified from ethyl acetate fraction of Quercus incana. The structure of these compounds is mainly established by using advanced spectroscopic technique such as UV, IR, one-dimensional (ID) and two-dimensional (2D) NMR techniques, and EI mass. The structural formula was deduced to be 4-hydroxydecanoic acid [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. Both isolated compounds were tested for their antimicrobial potential and showed promising antifungal activity against Aspergillus niger and Aspergillus flavus.

Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles.

In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 µM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 µM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 µM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 µM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of -10.19, -9.97, -9.68, and -11.03 Kcal.mol-1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of -9.9, -7.4, and -8.2 Kcal.mol-1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.

Isolation and characterization of three new anti-proliferative Sesquiterpenes from Polygonum barbatum and their mechanism via apoptotic pathway.

BACKGROUND: The emergence of chemoresistant cancers and toxicity related to existing chemotherapeutic agents, demand the search for new pharmacophore with enhanced anti-cancer activity and least toxicity. For this purpose, three new sesquiterpenes were isolated from ethyl acetate fraction of the aerial parts of the plant Polygonum barbatum and evaluated for their anti-cancer potential. METHODS: The structural elucidation and characterization of the isolated compounds 1-3 were performed using various spectroscopic techniques such as mass, UV, IR, and extensive 1D/2D-NMR spectroscopy. Furthermore, the compounds 1-3 were subjected to screening of anti-cancer activity against different cell lines followed by brief analysis of apoptotic and anti-angiogenic potentials of the potent hit against non-small cell lung carcinoma cell line. RESULTS: All the compounds 1-3 were subjected to anti-proliferative potential against non-small cell lung carcinoma (NCI-H460), breast cancer (MCF-7), cervical cancer (HeLa) and normal mouse fibroblast (NIH-3 T3) cell lines. Among these, compound 3 was found to be more cytotoxic against NCI-H460 and MCF-7 cells (IC50 = 17.86 ± 0.72 and 11.86 ± 0.46 µM respectively). When compared with the standard drug cisplatin compound 3 was found to have more potent activity against NCI-H460 (IC50 = 19 ± 1.24 µM) as compared to MCF-7 cell lines (IC50 = 9.62 ± 0.5 µM). Compound 3 induced apoptosis in NCI-H460 cells in a dose dependent manner. It significantly downregulated, the expression of anti-apoptotic (BCL-2 L1 and p53) and increased the expression of pro-apoptotic (BAK and BAX) genes. Besides apoptosis, it also significantly reduced the cell migration and downregulated the angiogenic genes (i.e. VEGF and COX-2), thereby, inhibiting angiogenesis in NCI-H460 cells. CONCLUSION: Compound 3 possesses potent anti-proliferative potential as well as induced apoptosis and inhibited the cell migration of the cancerous cells by altering the gene expression, responsible for it.

Antidepressent Effect of Two New Benzyl Derivatives from Wild Strawberry Fragaria vesca var. nubicola Lindl. ex Hook.f.

Two new benzyl derivatives were isolated from ethyl acetate fraction of wild strawberry, Fragaria vesca var. nubicola Lindl. ex Hook.f. The structures of these compounds were elucidated to be 5-(4-hydroxy-3-methoxyphenethyl)-7-methoxy-2H-chromen-3-ol (1) and 5-(4-hydroxy-3-methoxyphenethyl)-4,7-dimethoxy-2H-chromen-3-ol (2) based on spectroscopic data through IR, UV, 1H-NMR, 13C-NMR along with two dimensional (2D) techniques HMBC, HMQC, and COSY. Both compounds 1 and 2 were studied in tail suspension and forced swim tests for antidepressant like effects. A significant dose dependent antidepressant like effect was observed by causing spontaneous anti-immobility at various test doses upon intraperitoneal administration.