Observed IC50 Values Research Articles

Organocatalytic[3 + 2]Cycloaddition: Synthesis of Quinazoline Containing Sulfonyl 1,2,3‐Triazoles as Potent EGFR Targeting Anti‐Breast Cancer Agents

ABSTRACTA general strategy was developed for the synthesis of new fully decorated 1,2,3‐triazoles (4a–4m and 5a–5g) containing quinazolines from 1‐(4‐nitrophenyl)‐2‐(quinazolin‐8‐ylsulfonyl) ethan‐1‐one and several azides using Ramachary organocatalytic azide‐ketone cycloaddition method. This reaction is reported for the synthesis of fully substituted sulfonyl‐1,2,3‐triazolyl quinazolins at a temperature of 100°C and the yields of the products produced are satisfactory to excellent. In vitro anticancer activity of all these derivatives demonstrated that six compounds, 4d, 4f, 4i, 4j, 5d, and 5e, were effective against two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Compounds 4f, 4j, and 5d had more action against both cell lines than Erlotinib. Later, the findings of inhibitory assays of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e against the tyrosine kinase EGFR revealed that compound 5d proved more potent than the reference erlotinib, while 4f and 4j had comparable efficacy. In silico molecular docking studies were also performed on six strong medicines to identify interactions with the EGFR receptor, and the energy estimations were shown to be comparable with the observed IC50 values. Ultimately, using SWISS/ADME and pkCSM, the in silico pharmacokinetic profile of potent compounds 4d, 4f, 4i, 4j, 5d, and 5e was predicted. All of the compounds precisely followed the principles established by Lipinski, Veber, Egan, and Muegge.

Design, Synthesis, Characterization, and Cytotoxicity of New Pyrazolylmethylene-2-thioxoimidazolidin-4-one Derivatives towards Androgen-Sensitive LNCaP Prostate Cancer Cells.

A new class of pyrazolylmethylene-2-thioxoimidazolidin-4-one derivatives 3a-p were rationally designed and synthesized with the aim of exploring their potential as treatments for prostate cancer. The synthesized compounds 3a-p were biologically analyzed for their anticancer effects against AR+LNCaP, AR-PC-3, and Wi38 cell lines. The observed IC50 values against AR+LNCaP ranged between 10.27 ± 0.14 and 109.72 ± 2.06 µM after 24 h of incubation. Compounds 3i-k, 3m, and 3o-p recorded IC50 values of 05.22 ± 0.12 to 11.75 ± 0.07 µM after 48 h incubation in the presence of 1 nM DHT, with higher selectivity towards AR+LNCaP. Moreover, compounds 3i and 3k significantly induced Caspase 3 accumulation, reduced DNA content at the various stages of the cell cycle, and ultimately caused AR+LNCaP cell growth arrest, as confirmed by cell apoptosis assays. These findings suggest that these analogues of androgen receptor blockers have promising potential for further investigation as effective treatments for prostate cancer.

Nanoparticle-based delivery of harmine: A comprehensive study on synthesis, characterization, anticancer activity, angiogenesis and toxicity Evaluation

The effective treatment of cancer presents numerous challenges, including drug resistance and the risk of detrimental effects on normal tissues. Harmine, a beta-carboline alkaloid, has demonstrated diverse biological properties. This study aimed to synthesize and characterize harmine encapsulated in polylactic-co-glycolic acid (PLGA) nanoparticles (Ha-PLGA-NPs) to investigate their potential as agents against cancer and angiogenesis. The synthesized Ha-PLGA-NPs were thoroughly characterized, exhibiting a connected rod-shaped crystal which some retaining the spherical shape of nanoparticles with an average size of 302.96 nm. Furthermore, the nanoparticles demonstrated a dispersion index of 0.23 and a surface charge of −16.51 mV. In vitro cytotoxicity assays conducted on the breast cancer cell line (MCF-7) revealed that Ha-PLGA-NPs possessed significant cytotoxic properties, with an observed IC50 value of 87.74 μg/mL. Notably, no substantial cytotoxicity was observed in human foreskin fibroblasts, indicating a favorable selectivity towards cancer cells. Evaluation of the anti-angiogenic activity of Ha-PLGA-NPs demonstrated a concentration-dependent inhibition of angiogenesis. Mechanistic investigations indicated that the observed inhibition was mediated through the regulation of key genes involved in angiogenesis, including caspase 3, caspase 9, VEGF, and VEGF-R. In vivo studies involving dietary administration of Ha-PLGA-NPs in mice revealed improvements in weight gain, feed intake, liver enzyme levels, and redox potential. These findings underscore the potential of Ha-PLGA-NPs as a promising therapeutic agent for cancer treatment. The observed effects are attributed to their ability to induce programmed cell death and inhibit angiogenesis, thus offering a multifaceted approach to combat cancer.

Green synthesis, in silico modeling, and biological evaluation of N-substituted (Z)-5-arylidene imidazolidine/thiazolidine-2,4-dione/4-thione derivatives catalyzed by Bu SO3H core-shell nanostructures.

In this effort, the immobilization of guanidine-sulfonate on the surface of Fe3O4 MNPs (magnetic nanoparticles) as a novel acid nanocatalyst has been successfully reported for the synthesis of N-substituted (Z)-5-arylidene thiazolidine-2,4-dione and related cyclic derivatives, including rhodanine (RHD) and hydantoin (HYD) via a one-pot multiple-component reaction under green conditions. The products were characterized by SEM, TEM, TGA, EDS, BET techniques, VSM, and FTIR. The novel compounds synthesized using this methodology, designated as series La (1-9), Lb (1-8), and Lc (1-8), were subjected to anticancer screening against A549 and MCF7cell lines via MTT assays. Notably, several compounds (L1a, L2a, L3a, L1b, L2b, L3b, and L4b) exhibited potent antiproliferative activities, with observed IC50 values as low as 1.23 μM and 1.02 μM against MCF-7 cells, thereby outperforming the established anticancer drugs doxorubicin and cisplatin. Molecular docking and dynamics simulations revealed that ligands L1a, L2a, and L3a strongly interact with the protein target 3CD8, with L1a displaying significant hydrophobic and hydrogen bonding interactions and L2a engaging in unique pi-pi stacking with key residues. For protein 2WGJ, ligand L4b exhibited exceptional binding affinity, characterized by robust hydrogen bonding, hydrophobic interactions, and additional stabilizing mechanisms such as water bridges and pi interactions. Hence, N-substituted (Z)-5-arylidene thiazolidine-2,4-dione and its cyclic derivatives may serve as promising candidates for further exploration in the development of new multi-target cancer chemotherapy agents. These findings introduce promising anticancer agents and establish Fe3O4 MNPs as a versatile and environmentally sustainable catalytic platform in drug discovery.

Synthesis of Luotonin and Rutaecarpine Analogues by One‐Pot Intramolecular Dehydrogenative Cross‐Coupling and Benzylic C−H Oxidation, and In Vitro Cytotoxicity Assay

AbstractHerein, we reported an effective one‐pot protocol to synthesize quinazolinone fused N‐heterocyclic scaffold, structurally similar to the natural product Luotonin and Rutaecarpine by Pd(OAc)2/Ag(OAc)‐promoted intramolecular dehydrogenative cross‐coupling (DCC). The structure of all the compounds has been confirmed unambiguously by NMR, mass, and XRD. The electronic effect of the substituents attached to the backbone of the starting material was thoroughly investigated. The outcome of the reaction is highly dependent on the substrate structure and pH of the medium. Based on the experimental observation, a probable mechanism has been proposed. To see the anti‐cancer properties, we have studied concentration‐dependent cell viability assay of one compound on SiHa cell, a human cervical cancer cell line. The observed IC50 value was 23 μM.

Prospective in vitro A431 cell line anticancer efficacy of zirconia nanoflakes derived from Enicostemma littorale aqueous extract.

Biomedical applications of zirconia nanomaterials were limited in biological systems. In this research, 8-15 nm size zirconia nanoflakes (ZrNFs) were fabricated and their nature, morphology, and biocompatibility were evaluated. The synthesis was carried out using Enicostemma littorale plant extract as an effective reducing and capping agent. Physiochemical properties of prepared ZrNFs were characterized using diverse instrumental studies such as UV-vis spectrophotometer, Fourier-transform infrared, powder X-ray diffractometer, scanning electron microscope, transmission electron microscope (TEM), energy dispersive X-ray, and cyclic voltammetry (CV). The XRD pattern confirmed the tetragonal phases of ZrNFs and the highest crystallite size of Zr0.02, Zr0.02, and Zr0.06 was 56, 50, and 44 nm, respectively. The morphology of samples was assessed using TEM. Electrophysiological effects of ZrNFs in the cellular interaction process were revealed by the slower rate of electron transfer results in CV demonstration. Biocompatibility of synthesized ZrNFs was studied on A431 human epidermoid carcinoma epithelial cells. The cell viability was increased with an increasing the concentration of nanoflakes up to 6.50-100 μg/mL. The cell viability and observed IC50 values (44.25, 36.49, and 39.62 μg/mL) reveals that the synthesized ZrNFs using E. littorale extract is found to be efficient toxic to A431 cancer cell lines.

In vitro cytotoxicity and antimicrobial evaluation of novel 24–28 membered Schiff base octaazamacrocyclic complexes of manganese(II): Synthesis, characterization, DFT and molecular docking studies

The development of novel metal-based molecular antibiotics is an effective strategy to combat the rising threat of cancer and microbial diseases. In this view, novel Schiff base octaazamacrocyclic complexes of Mn(II) were synthesized using 2:2 molar ratio of macrocyclic ligands derived from Schiff base ligand [L] and dicarboxylic acids. The synthesized compounds were characterized by infra-red, 1H NMR, 13C NMR, ESI-mass, UV–visible, EPR, and powder X-ray diffraction spectral studies, together with elemental (CHN) analysis, molar conductance, and magnetic susceptibility measurements. Calculations based on density functional theory (DFT) help in determining the stability of synthesized macrocylic ligands. Electronic spectra led to the assignment of an octahedral geometry to the synthesized macrocyclic complexes. In vitro cytotoxicity of macrocyclic ligands and their Mn(II) complexes was examined against three distinct cancerous cell lines, including HeLa, A549, and MCF7 cells. The observed IC50 values for the tested compounds against cancerous cell lines demonstrate a relatively good level of cytotoxicity. Molecular docking of Schiff base macrocyclic ligands supported their cytotoxic potential against the tested cell lines. Moreover, the antimicrobial activity of the synthesized compounds was also evaluated against bacterial (E. coli, B. subtilis) and fungal strains (C. albicans, F. oxysporum). The results indicate that the macrocyclic Mn(II) complexes have more antimicrobial potential than macrocyclic ligands against tested pathogens.

Rationally Designed Minimal Bioactive Domains of AS-48 Bacteriocin Homologs Possess Potent Antileishmanial Properties.

Leishmaniasis, a category I neglected tropical disease, is a group of diseases caused by the protozoan parasite Leishmania species with a wide range of clinical manifestations. Current treatment options can be highly toxic and expensive, with drug relapse and the emergence of resistance. Bacteriocins, antimicrobial peptides ribosomally produced by bacteria, are a relatively new avenue for potential antiprotozoal drugs. Particular interest has been focused on enterocin AS-48, with previously proven efficacy against protozoan species, including Leishmania spp. Sequential characterization of enterocin AS-48 has illustrated that antibacterial bioactivity is preserved in linearized, truncated forms; however, minimal domains of AS-48 bacteriocins have not yet been explored against protozoans. Using rational design techniques to improve membrane penetration activity, we designed peptide libraries using the minimal bioactive domain of AS-48 homologs. Stepwise changes to the charge (z), hydrophobicity (H), and hydrophobic dipole moment (μH) were achieved through lysine and tryptophan substitutions and the inversion of residues within the helical wheel, respectively. A total of 480 synthetic peptide variants were assessed for antileishmanial activity against Leishmania donovani. One hundred seventy-two peptide variants exhibited 50% inhibitory concentration (IC50) values below 20 μM against axenic amastigotes, with 60 peptide variants in the nanomolar range. Nine peptide variants exhibited potent activity against intracellular amastigotes with observed IC50 values of <4 μM and limited in vitro host cell toxicity, making them worthy of further drug development. Our work demonstrates that minimal bioactive domains of naturally existing bacteriocins can be synthetically engineered to increase membrane penetration against Leishmania spp. with minimal host cytotoxicity, holding the promise of novel, potent antileishmanial therapies. IMPORTANCE Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. There are three primary clinical forms, cutaneous, mucocutaneous, and visceral, with visceral leishmaniasis being fatal if left untreated. Current drug treatments are less than ideal, especially in resource-limited areas, due to the difficult administration and treatment regimens as well as the high cost and the emergence of drug resistance. Identifying potent antileishmanial agents is of the utmost importance. We utilized rational design techniques to synthesize enterocin AS-48 and AS-48-like bacteriocin-based peptides and screened these peptides against L. donovani using a fluorescence-based phenotypic assay. Our results suggest that bacteriocins, specifically these rationally designed AS-48-like peptides, are promising leads for further development as antileishmanial drugs.

Phenyl boronic acid -PEG-stearic acid biomaterial-based and sialic acid targeted nanomicelles for colon cancer treatment

This study aims to develop and evaluate a sialic acid receptor-targeting biomaterial for an effective delivery of usnic acid (UA). The novel biomaterial system is composed of three different parts; (1) stearic acid (SA) a hydrophobic core for encapsulation of UA, (2) PEG spacer to make conjugate amphiphilic, and (3) at the periphery phenylboronic acid (PBA) for cancer cell targeting. The synthesized PBA-PEG-SA biomaterial was characterized by FTIR NMR, and MALDI-TOF analysis. An average molecular weight of PBA-PEG-SA was about 3896 Da. The PBA-PEG-SA biomaterial was self-assembled into the nanomicelles with a 460 μg/mL CMC value. The UA-loaded PBA-PEG-SA nanomicelles (UPNM) were analysed by DLS, TEM, FTIR NMR, DSC and XRD techniques. The average particle size of UPNM was about 160 nm and its spherical nature was confirmed by TEM analysis. The synthesized biomaterial provided a pH-sensitive and controlled release of encapsulated UA with < 10% release at gastric pH 1.2 while > 90% release at intestinal pH 6.8. In vitro cytotoxicity potential of developed UPNM was investigated against HCT116 human colon cancer cells. The in vitro results proved that the synthesized PBA-PEG-SA biomaterial had good biocompatibility and PBA decorated nanomicelles could be successfully uptaken by HCT116 cancer cells. The observed IC50 value for UPNM (5.37 ± 0.78 μg/mL) was significantly lower (p < 0.01) than pure UA (8.57 ± 0.26 μg/mL) or non-targeted UA-loaded nanomicelles (8.36 ± 0.63 μg/mL). Further, the targeted nanomicelles showed higher apoptosis and greater control over the colony formation ability of HCT116 cells than pure drug or non-targeted UA-loaded nanomicelles.

Chromatography analysis, in vitro antioxidant and antibacterial activities of essential oil of Artemisia herba-alba Asso of Boussaâda, Algeria

Abstract. Kadri M, Yahia A, Goubi S, Mekhedmi NE, Selmane M, Chemsa AE. 2022. Chromatography analysis, in vitro antioxidant and antibacterial activities of essential oil of Artemisia herba-alba Asso of Boussaâda, Algeria. Biodiversitas 23: 4424-4431. Artemisia herba-alba Asso (Asteraceae family) is widespread in the semi-arid and arid steppes of North Africa. This plant is used for traditional treatment. The present study aims to investigate the chemical composition, antioxidant and antimicrobial activities of A. herba-alba essential oil found in southwest Algeria (Boussaâda region). Artemisia herba-alba essential oil was obtained by hydrodistillation method, and its chemical composition was identified by using GC/MS analysis. In addition, the antioxidant activity of the extracted essential oil was determined using the DPPH assay. The antimicrobial activity of the essential oil was determined by the agar disc diffusion method. The essential oil extracted from the aboveground portions by hydrodistillation was analyzed by GC/MS. 38 components were identified, making up 69.37% of the oil, the most important of which is thujone (9.875%), camphor (3.762%), cis-p-menthadien-1-of (3.572%), and isoborneol (2.334%). The observed IC50 values of the DPPH assay were 7.31 ± 0.088 mg/mL. On the other hand, this oil was active against all strains tested, this activity varied from 12.77 ± 0.510 mm on Listeria innocua CIP 74915. These results demonstrate that the plant tested could be a potential source of natural antioxidants and antimicrobial agents.

Spectroscopic investigations, ab-initio DFT calculations, molecular docking and in-vitro assay studies of novel oxovanadium(V)chalcone complexes as potential antidiabetic agents

A series of four novel oxovanadium(V)chalcone complexes ([VO(LI-IV)2Cl]; where HLI=1-(2-Hydroxy-phenyl)-3-phenyl-propenone, HLII=1-(1-Hydroxy-naphthalen-2-yl)-3-phenyl-propenone, HLIII = 1-(2-Amino-phenyl)-3-phenyl-propenone, HLIV = 4-Hydroxy-6-methyl-3-(3-phenyl-acryloyl)-pyran-2-one) were designed and synthesized by performing chemical reaction between VOCl3 and respective chalcone derivatives in 1:2 molar ratio. Their formation as well as chemical structures were confirmed by FTIR, UV-Visible, 1H-NMR, SEM, EDS, and mass spectrometry spectroscopic techniques. The geometry of the synthesized complexes was purposed to be octahedral on the basis of the characterization. Further computational and structural parameters of the synthesized complexes were determined in order to establish their thermodynamic stability/chemical reactivity of the synthesized complexes. Density Functional Theory (DFT) method was employed to calculate the molecular geometry and vibrational frequencies of the synthesized complexes using B3LYP hybrid functional at 6-31G* level of basis set. Further, Spartan'20 V1.0.0 program package was used to calculate the 1H-NMR spectra with (DFT/ B3LYP) in the gaseous phase to validate the structure of oxovanadium(V) complexes. The experimentally obtained results were found to be well correlated with theoretical results with a correlation value > 0.96. Global reactivity descriptors helps to explain the bioactivity of complexes hence, were calculated from the HOMO-LUMO energies. The enzymatic assay experiments indicated that all the four synthesized complexes have significant to moderate inhibition potential against α-glucosidase, and α-amylase enzymes. Among all the oxovanadium(V)chalcone complexes, complex 4showed excellent and superior inhibition potency almost equivalent to the commercially available Acarbose drug and even better in case of α-amylase. The observed IC50 value of complex 4 for the inhibition of α-amylase and α-glucosidase was calculated to be 16.36 µg/mL and 57.27 µg/mL, respectively. The Kinetic parameters calculated from the Lineweaver-Burk plot showed that complex 4 were uncompetitive and mixed inhibitor of α-amylase and α-glucosidase respectively. Thereafter,the antiradical activity of synthesized vanadium(V)chalcone complexes was assessed with the help of DPPH radical scavenging assay. The results demonstrated that all the complexes were remarkable free radical scavengers for the DPPH. The complex 1 was observed to be best among them with the 0.03 µg/mL IC50 value. The AutoDockTools-1.5.6 software was used to examine structure-activity relationship and the binding interactions between oxovanadium(V) complexes and protein target alpha-amylase, alpha-glucosidase, and Myeloperoxidase respectively. The in-vitro as well as in-silico biological activity studies showed significant and major improvements after complexation of chalcone derivatives with vanadium oxychloride (VOCl3). Thus, oxovanadium(V)chalcone complexes were found to be potent inhibitors of the α-glucosidase and α-amylase enzyme.

Response of denitrifying anaerobic methane oxidation enrichment to salinity stress: Process and microbiology

Denitrifying anaerobic methane oxidation (DAMO) is a novel biological process which could decrease nitrogen pollution and methane emission simultaneously in wastewater treatment. Salinity as a key environmental factor has important effects on microbial community and activity, however, it remains unclear for DAMO microorganisms. In this study, response of the enrichment of DAMO archaea and bacteria to different salinity was investigated from the aspect of process and microbiology. The results showed that the increasing salinity from 0.14% to 25% evidently deteriorated DAMO process, with the average removal rate of nitrate and methane decreased from 1.91 mg N/(L·d) to 0.07 mg N/(L·d) and 3.22 μmol/d to 0.59 μmol/d, respectively. The observed IC50 value of salinity on the DAMO culture was 1.73%. Further microbial analyses at the gene level suggested that the relative abundance of DAMO archaea in the enrichment decreased to 46%, 39%, 38% and 33% of the initial value. However, DAMO bacteria suffered less impact with the relative abundance maintaining over 75% of the initial value (except 1% salinity). In functional genes of DAMO bacteria, pmoA, decreased gradually from 100% to 86%, 43%, 15% and 2%, while mcrA (DAMO archaea) maintained at 67%–97%. This difference probably indicated DAMO bacteria appeared functional inhibition prior to community inhibition, which was opposite for the DAMO archaea. Results above-mentioned concluded that, though the process of nitrate-dependent anaerobic methane oxidation was driven by the couple of DAMO archaea and bacteria, they individually featured different response to high salinity stress. These findings could be helpful for the application of DAMO-based process in high salinity wastewater treatment, and also the understanding to DAMO microorganisms.

Phytochemical Profiling, Anti-Inflammatory, Anti-Oxidant and In-Silico Approach of Cornus macrophylla Bioss (Bark)

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla. C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC50 values of 09.54 μg/mL and 7.8 μg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla, Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC50 values were 93.35 μg/mL against COX-2 and 75.64 μg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future.

Synthesis, NMR, anti-oxidant, anti-cancer activity, Molecular docking, DFT Calculations and in silico ADME analysis of 3′-benzoyl-4′-phenyl-5′-(piperazin-1-ylmethyl)spiro[indoline-3,2′-pyrrolidin]-2-one derivatives

A series of seven novel spirooxindoles derivatives were synthesized by a three-component 1,3-dipolar cycloaddition method. The reaction proceeds through the formation of azomethine ylides generated in situ by the decarboxylative condensation of isatin and amine with dipolarophile chalcones. The antioxidant results revealed that the IC50 value of compounds 4a,4b,4d and 4f are very excellent against hydroxyl radical (IC50 = 15.9 to 30.3 µg/ml) and superoxide radical scavenging activity (IC50 = 14.7 to 22.2 µg/ml) whereas standard antioxidant Vitamin C showed their IC50 value only in the range of 25.0 and 20.0 µg/ml. Cytotoxic activity by MTT assay revealed that the compounds 4a,4b,4d and 4f exhibited broad inhibition on the KB cell lines with IC50 values of 6.5, 9.5, 32.5 and 55 µM, respectively. The observed IC50 values revealed that compound 4b possessed more inhibitory effect against the cancer cells. The anticancer activities of these derivatives were studied using molecular docking studies and it is compared with their experimental results. In addition, good oral bioavailability was predicted for all compounds by in silico calculations of ADME (absorption, distribution, metabolism, and elimination) and pharmacokinetic parameters. Finally the geometrical structure was optimized by density functional theory (DFT) method at B3LYP/6–31 G (d, p) as the basic set. The HOMO-LUMO energies describe the charge transfer takes place within the molecule. Molecular electrostatic potential has been analyzed.

Phytochemistry, anti-diabetic and antioxidant potentials of Allium consanguineum Kunth

AimThe study was planned to investigate the phytochemicals, antidiabetic and antioxidant studies of A. consanguineum.MethodsThe preliminary studies were performed on crude extract and different solvent fractions. Based on the potency, the chloroform fraction was semi-purified to phyto-fractions CHF-1 – 5. Furthermore, CHF-3 was subjected to isolation of pure compounds using column chromatography. The α-glucosidase, α-amylase and antioxidant assays (DPPH, ABTS, H2O2) were performed on all samples. The in-vivo experiments on compounds 1 and 2 were also performed using oral glucose tolerance test. Docking studies were performed on α-glucosidase and α-amylase targets.ResultsAmong all fractions, the chloroform fraction exhibited excellent activities profile giving IC50 values of 824, 55, 117, 58 and 85 μg/ml against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 targets respectively. Among the five semi-purified chloroform phyto-fractions (CHF-1-5), CHF-3 was the leading fraction in activities giving IC50 values of 85.54, 61.19 and 26.58 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Based on the overall potency and physical amount of CHF-3, it was subjected to purification to get compounds 1 and 2. The two compounds were also found potent in in-vitro activities. The observed IC50 values for compound 1 were 7.93, 28.01 and 6.19 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Similarly, the compound 2 exhibited IC50 of 14.63, 24.82 and 7.654 μg/ml against α-glucosidase, α-amylase and DPPH respectively. Compounds 1 and 2 were potent in decreasing the blood glucose levels in experimental animals. Compounds 1 and 2 also showed interactions with the respective enzymes with molecular docking.ConclusionsWe can conclude that A. Consanguineum is a rich source of natural antidiabetic agents. Bioguided isolation of compound 1 and 2 showed potential inhibitions in all tested in-vitro antidiabetic targets. Further, both the compounds were also able to decrease the blood glucose levels in experimental animals.

The Antimicrobial Efficacy Against Selective Oral Microbes, Antioxidant Activity and Preliminary Phytochemical Screening of Zingiber officinale.

IntroductionGinger (Zingiber officinale) has been one of the most commonly consumed herbal medicines for a long time to treat several common diseases. Antibacterial activity, antioxidant properties and many bioactive compounds in ginger have been identified previously, which could be used as an alternative method to treat many infectious diseases.MethodsThe current study evaluates ginger’s biochemical profile using qualitative and quantitative analysis and its bioactive potentials using antioxidant and antimicrobial assays against Streptococcus mutans and selective oral microbes. HPLC analysis was performed for the quantitative analysis. DPPH and disc diffusion assays were used for antioxidant and antimicrobial activities. The antimicrobial activity was checked against Streptococcus mutans, Enterococcus faecalis, Staphylococcus spp., and Lactobacillus spp. All solvents were removed by rotary evaporation before testing the dried extracts.ResultsThe observed IC50 value showed that distilled water extract exhibited the highest antioxidant activity (43.9), followed by ethanol extract (52.4), and the lowest activity was observed in n-butanol extract (91.2) and n-hexane (90.6). Different plant extracts have shown significant antibacterial activity (p = 0.001) against each bacterium. The highest antibacterial activity against tested bacteria was observed in n-hexane, chloroform and ethanol extracts. In comparison, the ethyl acetate, n-butanol and water extracts showed low antibacterial activity.ConclusionThis study emphasizes that Zingiber officinale (Z. officinale) against Gram-positive bacteria is an effective antimicrobial herb. Furthermore, it can be used as a potential natural source of antioxidants. Further studies on the toxicity analysis of ginger are recommended.

POTENTIALLY ACTIVE METAL OF COBALT, COPPER AND ZINC COMPLEXES DERIVED FROM SCHIFF BASE LIGAND OF 3-ETHOXY-2-HYDROXY-BENZALDEHYDE AND ANILINE FOR THEIR ANTICANCER ACTIVITY

New Schiff base transition metal complexes derived from 3-ethoxy-2-hydroxy-benzaldehyde and aniline were characterized by magnetic susceptibility measurements, molar conductance, MS, FT-IR, 1H-NMR, 13C-NMR, Absorbance and EPR spectra. The spectral evidences clearly showed that all the metal chelates distorted octahedral geometry except Zn(II) complex which exist square planar geometry. Electron Spin Resonance (ESR) spectrum of [CuL] complex was coinciding with proposed geometries and other reported complexes. All the synthesized compounds were studied for anticancer studies by MTT method using Hela cells. From anticancer activities, the observed IC50 values of synthesized complexes are significantly higher than standard Cis-platin. The cytotoxicity of the tested compounds against the Hela cell line pursued their order Co(II) &gt; Cu(II) &gt; Zn(II) &gt; ligand. Among them, Co(II) complex showed higher cytotoxic activity than other complexes and Schiff base.

Microsphere Peptide-Based Immunoassay for the Detection of Recombinant Bovine Somatotropin in Injection Preparations.

The use of peptides in immunoassays can be favored over the use of the full protein when more cost effective or less toxic approaches are needed, or when access to the full protein is lacking. Due to restricted access to recombinant bovine somatotropin (rbST), a protein enhancing growth and lactating performances of livestock, which use has been banned in the EU, Canada and Australia (amongst others), we developed a peptide-based biorecognition assay on an imaging planar array analyzer. For this, we identified the rbST epitope that is responsible for binding to the rbST-targeting monoclonal antibody 4H12 (MAb 4H12) to be 115DLEEGILALMR125. This linear peptide was synthesized and coupled to microspheres, after which it was tested in a biorecognition competitive inhibition assay format. We observed IC50 values of approximately 0.11 μg mL−1, which are lower than observed for the full rbST protein (IC50 = 0.20 μg mL−1). Importantly, there was no binding with the scrambled peptide. Preliminary results of directly coupled peptides in a microsphere biorecognition assay for detection of rbST are presented. Real-life applicability for detection of somatotropins (STs) in injection preparations of bovine-, porcine- and equine ST are shown. This newly developed immunoassay strongly supports future developments of peptide-based immunoassays to circumvent the limited access to the full protein.

Design and Synthesis of Novel Podophyllotoxins Hybrids and the Effects of Different Functional Groups on Cytotoxicity.

Development of novel anticancer therapeutic candidates is one of the key challenges in medicinal chemistry. Podophyllotoxin and its derivatives, as a potent cytotoxic agent, have been at the center of extensive chemical amendment and pharmacological investigation. Herein, a new series of podophyllotoxin-N-sulfonyl amidine hybrids (4a–4v, 5a–5f) were synthesized by a CuAAC/ring-opening procedure. All the synthesized podophyllotoxins derivatives were evaluated for in vitro cytotoxic activity against a panel of human lung (A-549) cancer cell lines. Different substituents’, or functional groups’ antiproliferative activities were discussed. The –CF3 group performed best (IC50: 1.65 μM) and exhibited more potent activity than etoposide. Furthermore, molecular docking and dynamics studies were also conducted for active compounds and the results were in good agreement with the observed IC50 values.

Crude extract and isolated bioactive compounds from Notholirion thomsonianum (Royale) Stapf as multitargets antidiabetic agents: in-vitro and molecular docking approaches

BackgroundDiabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus.MethodsThe crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B.ResultsInitially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70, < 0.1, 89 and 16 μg/mL against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 respectively. Three compounds (Nt01, Nt02 and Nt03) were isolated from Nt.EtAc of N. thomsonianum. The isolated compounds Nt01, Nt02 and Nt03 exhibited IC50 values of 58.93, 114.93 and 19.54 μM against α-glucosidase, while 56.25, 96.54 and 24.39 μM against α-amylase respectively. Comparatively, the standard acarbose observed IC50 values were 10.60 and 12.71 μM against α-glucosidase, α-amylase respectively. In PTP1B assay, the compounds Nt01, Nt02 and Nt03 demonstrated IC50 values of 12.96, 36.22 and 3.57 μM in comparison to the standard ursolic acid (IC50 of 3.63 μM). The isolated compounds also gave overwhelming results in DPPH assay. Molecular docking based binding interactions for α-glucosidase, α-amylase and PTP1B were also encouraging.ConclusionsIn the light of current results, it is obvious that N. thomsonianum is potential medicinal plant for the treatment of hyperglycemia. Overall, Nt.EtAc was dominant fraction in all in-vitro activities. Three compounds Nt01, Nt02 and Nt03 were isolated from ethyl acetate fraction. The Nt03 specifically was most potent in all in-vitro assays. The molecular docking studies supported our in-vitro results. It is concluded that N. thomsonianum is a rich source of bioactive antidiabetic compounds which can be further extended to in-vivo based experiments.