Phenolic composition,antioxidant and enzyme inhibitory activities of Parkia biglobosa (Jacq.) Benth., Tithonia diversifolia (Hemsl) A. Gray,and Crossopteryx febrifuga (Afzel.) Benth

Medicinal plants from Chad grow under special climatic conditions in between the equatorial forest of Central Africa and the desert of North Africa and are understudied. Three medicinal plants from Chad (T. diversifolia, P. Biglobosa and C. Febrifuga) were evaluated for their phenolic composition, antioxidant and enzyme inhibition activities. The total phenolic composition varied from 203.19 ± 0.58 mg GAE/g DW in the ethyl acetate extract of P. biglobosa, to 56.41 ± 0.89 mg GAE/g DW in the methanol extract of C. febrifuga while the total flavonoid content varied from 51.85 ± 0.91 mg QE/g DW in the methanol extract of P. biglobosa to 08.56 ± 0.25 mg QE/g DW in the methanol extract of C. febrifuga. HPLC-DAD revealed that rutin, gallic acid and protocatechuic acid were the most abundant phenolics in T. diversifolia, P. Biglobosa and C. Febrifuga respectively. The antioxidant activity assayed by five different methods revealed very good activity especially in the DPPH^?, ABTS^?+ and CUPRAC assays where the extracts were more active than the standard compounds used. Good inhibition was exhibited against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with methanol (IC₅₀: 15.63 ± 0.72 µg/mL), ethyl acetate (IC₅₀: 16.20 ± 0.67 µg/mL) extracts of P. biglobosa, and methanol (IC₅₀: 21.53 ± 0.65 µg/mL) and ethyl acetate (IC₅₀: 30.81 ± 0.48 µg/mL) extracts of T. diversifolia showing higher inhibition than galantamine (IC₅₀: 42.20 ± 0.44 µg/mL) against BChE. Equally, good inhibition was shown on α-amylase and α-glucosidase. On the α-glucosidase, the ethyl acetate (IC₅₀ = 12.47 ± 0.61 µg/mL) and methanol extracts (IC₅₀ = 16.51 ± 0.18 µg/mL) of P. biglobosa showed higher activity compared to the standard acarbose (IC₅₀ = 17.35 ± 0.71 µg/mL) and on α-amylase, the ethyl acetate (IC₅₀ = 13.50 ± 0.90 µg/mL) and methanol (IC₅₀ = 18.12 ± 0.33 µg/mL) extracts of P. biglobosa showed higher activity compared to acarbose (IC₅₀ = 23.84 ± 0.25 µg/mL). The results indicate that these plants are good sources of antioxidant phenolics and can be used to manage oxidative stress linked illnesses such as Alzheimer’s disease and diabetes.     

Design,synthesis of new novel quinoxalin-2(1H)-one derivatives incorporating hydrazone,hydrazine, and pyrazole moieties as antimicrobial potential with in-silico ADME and molecular docking simulation

A series of 6-(morpholinosulfonyl)quinoxalin-2(1H)-one based hydrazone, hydrazine, and pyrazole moieties were designed, synthesized, and evaluated for their in vitro antimicrobial activity. All the synthesized quinoxaline derivatives were characterized by IR, NMR (¹H /¹³C), and EI MS. The results displayed good to moderate antimicrobial potential against six bacterial, and two fungal standard strains. Among the tested derivatives, six quinoxalin-2(1H)-one derivatives 4a, 7, 8a, 11b, 13, and 16 exhibited a significant antibacterial activity with MIC values (0.97–62.5 µg/mL), and MBC values (1.94–88.8 µg/mL) compared with Tetracycline (MICs = 15.62–62.5 µg/mL, and MBCs = 18.74–93.75 µg/mL), and Amphotericin B (MICs = 12.49–88.8 µg/mL, and MFC = 34.62–65.62 µg/mL). In addition, according to CLSI standards, the most active quinoxalin-2(1H)-one derivatives demonstrated bactericidal and fungicidal behavior. Moreover, the most active quinoxaline derivatives showed a considerable antibacterial activity with bactericidal potential against multi-drug resistance bacteria (MDRB) strains with MIC values ranged between (1.95–15.62 µg/mL), and MBC values (3.31–31.25 µg/mL) near to standard Norfloxacin (MIC = 0.78–3.13 µg/mL, and MBC = 1.4–5.32 µg/mL. Further, in vitro S. aureus DNA gyrase inhibition activity were evaluated for the promising derivatives and displayed potency with IC₅₀ values (10.93 ± 1.81–26.18 ± 1.22 µM) compared with Ciprofloxacin (26.31 ± 1.64 µM). Interestingly, these derivatives revealed as good immunomodulatory agents by a percentage ranging between 82.8 ± 0.37 and 142.4 ± 0.98 %. Finally, some in silico ADME, toxicity prediction, and molecular docking simulation were performed and showed a promising safety profile with good binding mode.     

Polarity-guided phytochemical extraction,polyphenolic characterization,and multimode biological evaluation of Seriphidium kurramense (Qazilb.) Y. R. Ling

Purpose of studyThe undertaken study aims to assess the polyphenolic profile, and antioxidant, antimicrobial, antiviral, antidiabetic, and cytotoxic potential of Seriphidium kurramense (Qazilb.) Y. R. Ling extracts.MethodsExtracts of aerial parts were prepared by successive extraction (n-hexane {Sk-nH}, ethyl acetate {Sk-EA}, methanol {Sk-M} and aqueous {Sk-Aq}). Chromogenic assays determined the antioxidant profile while HPLC quantified several polyphenols. Agar well diffusion was employed for antimicrobial potential while brine shrimp and hemolytic assays established the biosafety profile.ResultsThe results have shown that maximum extract recovery (17.49% w/w), total phenolics content (24.44 ± 0.15 μg GAE/mgE), and total flavonoids content (6.87 ± 0.25 μg QE/mgE) were recorded in Sk-Aq. RP-HPLC quantified a significant amount of syringic acid (1.43 ± 0.05 µg/mgE), caffeic acid (0.48 ± 0.02 µg/mgE), gentisic acid (6.44 ± 0.01 µg/mgE), and quercetin (4.39 ± 0.01 µg/mgE) in Sk-Aq, while maximum amounts of thymoquinone (0.21 ± 0.02 µg/mgE) and luteolin (3.90 ± 0.03 µg/mgE) along with apigenin (3.72 ± 0.03 µg/mgE) existed in Sk-M and highest quantities of ferulic acid (2.98 ± 0.01 µg/mgE), myricetin (1.04 ± 0.02 µg/mgE) and kaempferol (1.23 ± 0.01 µg/mgE) were found to be present in Sk-EA. A substantial free radical scavenging (85.87 ± 1.00%), total reducing power (211.93 ± 0.97 µg AAE/mgE), and urease inhibition activity (87.99 ± 0.19% at 500 µg/ml) were also recorded in the Sk-Aq. The highest antioxidant capacity (243.5 ± 1.12 µg AAE/mgE), antibacterial, antifungal, and antiviral activity (100% reduction in plaque formation at 400 µg/ml) were observed for Sk-EA. Maximum antibacterial and antifungal activities were revealed against Klebsiella pneumoniae (MIC = 25 ± 0.37 µg/ml), and Candida albicans (MIC = 50 ± 0.19 µg/ml) respectively. The prominent antidiabetic potential was displayed by Sk-nH in terms of α-amylase and α-glucosidase inhibition.ConclusionThe results reported, herein suggest that S. kurramense can be a promising candidate for antioxidant, antibacterial, antifungal, antiviral, and antidiabetic secondary metabolites.     

Total phenolic and flavonoid contents,antioxidant, antidiabetic and antiplasmodial activities of Garcinia forbesii King: A correlation study

Garcinia forbesii King belongs to Clusiaceae is a source of secondary metabolites especially xanthones with various biological activities. G. forbesii King is also known for its empirical use for malaria and diabetes. This study investigated the total phenolic and flavonoid contents, in vitro antioxidant, antidiabetic and antiplasmodial activities of four extracts attained from the stem bark of G. forbesii King. The total phenolic and flavonoid contents were determined by spectrophotometric methods and antioxidant activity was evaluated by DPPH, ABTS, FRAP assays. In vitro antidiabetic activity was assessed by α-glucosidase and α-amylase assays and antiplasmodial activity was studied against chloroquine sensitive Plasmodium falciparum strain 3D7. The highest value of total phenolic (187.37 ± 0.06 mg GAE/g) and flavonoid (35.97 ± 0.02 mg QE/g) contents were recorded in n-hexane and methanolic extracts. n-Hexane extract showed the highest DPPH activity with IC₅₀ of 8.12 ± 0.02 μg/mL. Ethyl acetate extract exhibited better scavenging ability for ABTS with IC₅₀ of 3.88 ± 0.04 μg/mL. The FRAP assay showed better activity in methanol extract with an inhibition value of 73.68 ± 3.66 µM Fe²⁺/g. The strong inhibition against α-glucosidase and α-amylase were displayed by dichloromethane extract with IC₅₀ of 35.13 ± 2.01 μg/mL and 4.83 ± 0.20 μg/mL. n-Hexane and methanol extracts showed significant antiplasmodial activity with IC₅₀ of 0.23 ± 0.01 μg/mL and 0.73 ± 0.01 μg/mL, respectively. The correlation analysis indicated a positive relationship of total phenolic and flavonoid contents with antiplasmodial activity. The results revealed that n-hexane and methanol extracts could be used as a potential natural antiplasmodial, while dichloromethane extract is a promising natural antidiabetic.     

Phytochemical prospection,evaluation of antibacterial activity and toxicity of extracts of Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz

Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz is a arboreal species found in the Caatinga from Northeast of Brazil that has been used in popular medicine as an anti-inflammatory, healing, analgesic and for the treatment of respiratory system disorders. Therefore, the objective of this work was to evaluate the composition of ethanol extracts from the leaves and inner bark of Libidibia ferrea, as well as to verify its antibacterial activity and as a potential inhibitor of the TetK efflux pump in Staphylococcus aureus strains, in addition to investigating the toxicity of the extracts in a Drosophila melanogaster model. The analysis and quantification of the extracts markers was performed by High Performance Liquid Chromatography (HPLC). To determine the Minimum Inhibitory Concentration (MIC) broth microdilution tests were carried out. The evaluation of efflux pump inhibition was performed by modifying the MIC of antibiotics and ethidium bromide. Mortality and negative geotaxis tests were used to verify the toxicity of extracts on D. melanogaster. Hydrolysable tannins (gallic acid and ellagic acid) and flavonoids were found in HPLC analysis. The extracts did not show antibacterial activity, demonstrating a MIC ≥ 1024 µg/mL, however the ethanolic extract of the leaves decreased the MIC of the antibiotic from 64 µg/mL to 16 µg/mL, but this effect is not associated with the inhibition of the efflux pump. The extracts did not show toxicity in a D. melanogaster model. This is the first study to evaluate the antibacterial activity of L. ferrea extracts on the IS-58 strain of S. aureus, as well as the first to investigate its toxicity using D. melanogaster. From the results, further studies are needed to determine the mechanisms of action of the extract with other antibiotics.     

GC/MS and LC-MS/MS phytochemical evaluation of the essential oil and selected secondary metabolites of Ajuga orientalis from Jordan and its antioxidant activity

The current investigation aimed to shed light in the volatile and non-volatile secondary metabolites of Ajuga orientalis L. from Jordan. GC/MS and GC/FID analysis of the hydrodistilled essential oil obtained from aerial parts of the plant revealed tiglic acid (18.90 %) as main constituent. Each of the methanol and butanol fractions of A. orientalis were screened for their total phenol content (TPC), total flavonoid content (TFC), and antioxidant activity determined by DDPH and ABTS methods. The extracts were then analyzed by LC-ESI-MS/MS to unveil their chemical constituents, especially phenols and flavonoids. Results showed that the AO-B extract had the highest TPC (217.63 ± 2.65 mg gallic acid/g dry extract), TFC (944.41 ± 4.77 mg quercetin /g dry extract), highest DPPH and ABTS antioxidant activity ((4.00 ± 0.20) × 10^-2; (3.00 ± 0.20) × 10^-2 mg/mL, respectively) as compared to the AO-M extract. LC-ESI-MS/MS analysis of both extracts revealed the presence of several phenolics, flavonoids and nonphenolic acids.     

Ecofriendly synthesis of silver nanoparticles using Kei-apple (Dovyalis caffra) fruit and their efficacy against cancer cells and clinical pathogenic microorganisms

Green fabrication has become a safe approach for producing nanoparticles. Plant-based biogenic synthesis of silver nanoparticles (AgNPs) has emerged as a possible alternative to traditional chemical production. In this paper, we provide a low-cost, green synthesis of AgNPs utilizing using Kei-apple (Dovyalis caffra) fruit extract. Ultraviolet–visible (UV–Vis) spectroscopy, Fourier Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), X-Ray Diffraction (XRD), Scanning-Electron Microscope (SEM), and Dynamic Light Scattering (DLS) analyses were used to characterize green produced AgNPs. The formation of AgNPs was shown to have a surface resonance peak of 415 nm in UV–visible spectra, and FTIR spectra verified the participation of biological molecules in Synthesis of AgNPs. The TEM revealed that the biosynthesized AgNPs were mostly spherical in form, with size range of 12–53 nm. XRD diffractogram was used to demonstrate the face cubic centre (fcc) character of AgNPs. Excellent anticancer activity of AgNPs was recorded where more than 80% of Prostate Cancer (PC-3) cell lines was inhibited by 100–150 µg/mL of AgNPs, while 38% only was recorded using AgNO₃ and 55.62% was recorded D. caffra fruit extract at 150 µg/mL. Destructions of PC-3 cell was observed as a result of exposed to AgNPs, followed by D. caffra fruit extract, while minor alterations were recorded as exposed to AgNO₃. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging using AgNPs was three fold using fruit extract at 100 µg/mL indicating good antioxidant activity. Excellent inhibitory activity of AgNPs was recorded against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Aspergillus fumigatus with inhibition diameter zone 28.22 ± 0.25 mm, 23.21 ± 0.35 mm, 27.25 ± 0.03 mm, 28.40 ± 0.15 mm, 29.23 ± 0.44 mm, and 9.52 ± 0.5 mm, respectively compared with AgNO₃. D. caffra fruits considered a promising and safe source for fabrication of AgNPs with multi-biological functions.     

Spectrochemical analysis using LIBS and ICP-OES techniques of herbal medicine (Tinnevelly Senna leaves) and its anti-cancerous/antibacterial applications

Tinnevelly senna leaves are being applied to cure many diseases especially in developing countries and sub-Saharan region due to many bioactive compounds such as sennosides, phenols, and flavonoids. The conventional methods to isolate and analyze plant extracts biomolecules are not very effective as well cost effective as they require hazardous chemical solvents and reagents, which are time-consuming processes. The major objective of the present study is to investigate the feasibility of the Laser induced breakdown spectroscopy (LIBS) technique for rapid, eco-friendly, and multi-elemental analysis of Senna leaves extracts and study their antibacterial and anticancer potentials. The elegant LIBS technique was applied as a qualitative and quantitative method for Senna leaves sample’s elemental analysis and their biological activities were measured by evaluating anti-cancer and anti-bacterial analysis. The quantitative analysis of Senna leaves extracts was done using the calibration-free laser-induced breakdown spectroscopy (CF-LIBS) algorithm showing their appreciable content of several nutrient elements, and the obtained results were in close conformity with these achieved by using the standard analytical ICP OES technique. We studied the bactericidal efficacy of the Senna leaves extract against Staphylococcus aureus (S. aureus) by AWD assays and morphogenesis by scanning electron microscopy (SEM) and the anticancer activity was also investigated where different concentrations of Senna leaves extract were tested on cancer cells (HCT-116 and HeLa) and normal cells (HEK-293) using the cell metabolic activity MTT assay and Propidium iodide (PI) staining. We have also calculated the inhibitory concentration (IC50) value for the various extracts concentrations (25 µg/ml, 50 µg/ml, 100 µg/ml, 150 µg/ml, 200 µg/ml, and 225 µg/ml). We have found that IC₅₀ value for HCT-116 cells were 13.5 µg/ml, 17.5 µg/ml, 21.5 µg/ml, 22.5 µg/ml, 26 µg/ml and 33.5 µg/ml and for HeLa cells 15.25 µg/ml, 21.25 µg/ml, 23.5 µg/ml, 262.5 µg/ml, 36.25 µg/ml, and 39.50 µg/ml. The bactericidal efficacy of the Senna leaves extract showed significant inhibition against Gram-positive bacterium. Both MTT and PI analysis showed that Senna leaves extract induced profound inhibition on HCT-116 growth and proliferation. Additionally, Senna leaves extract did not exert an inhibitory influence on normal (HEK-293), which is non-cancerous cells. We suggest that the extract specifically targets the cancerous cells, which could be highly beneficial for the development of future safe anticancer and antibacterial drugs using these extracts.     

Chemical profiling of Aristolochia tagala Cham. leaf extracts by GC-MS analysis and evaluation of its antibacterial activity

Aristolochia tagala Cham. (Aristolochiaceae) is an underexplored medicinal plant traditionally used to treat snakebites, stomachaches, and poisonous bites. In this study, chemical profiling of the petroleum ether, chloroform, ethyl acetate, methanol, and hydro-alcoholic extracts of the plant was investigated by gas chromatography-mass spectrometry. The antibacterial activity of the plant was tested against ten bacterial strains using the agar disc diffusion and microdilution method. In total, forty two compounds were identified from the extracts with neophytadiene, palmitic acid, phytol, trans-δ9-octadecenoic acid, phytyl palmitate, phytyl tetradecanoate, ergost-5-en-3-ol, (3beta,24r)-,z,z-8,10-hexadecadien-1-ol, stigmasterol, and tetrapentacontane as major phytoconstituents. The hydro-alcoholic extract possessed maximum total phenolics (52.58 ± 06 mg GAE/g), total flavonoids (48.66 ± 91 QRE/g), total flavanols (67.20 ± 64 QRE/g) and vitamin E content (31.26 ± 0.05 mg ATE/g). For antibacterial activity, hydro-alcoholic extract of Aristolochia tagala effectively controlled the growth of bacterial strains such as Proteus valgaris (26.3 mm) and Pseudomonas aeruginosa (19.33 mm) and the same extract showed notable minimum inhibitory concentration (MIC) against the growth of bacteria like Escherichia coli (10.93 μg/ml) and Enterobacter aerogenes (43.7 μg/ml). It was determined that, hydro-alcoholic and methanolic extracts Aristolochia tagala leaf found to have a number of bioactive compounds with significant antibacterial activity against the pathogenic bacteria. Further investigations are necessary to isolate and characterize bioactives and to evaluate its therapeutic potential.     

Phytochemical and Biological Characterization of Tephrosia nubica Boiss. Growing in Saudi Arabia

The chloroform (TNC), ethyl acetate (TNE) and n-butanol (TNB) fractions of Tephrosia nubica Bioss. growing in Saudi Arabia were investigated for the first time using UPLC-ESI-MS/MS in two ionization modes. The analysis revealed the tentative identification of 107 compounds. Moreover, the therapeutic potential of T. nubica fractions was determined by in vitro evaluation of their cytotoxic, antioxidant, and anti-obesity activities using MTT assay, DPPH radical scavenging activity and pancreatic lipase inhibitory assay, respectively. The results showed that TNE, TNB, TNC fractions revealed weak antioxidant activity with SC₅₀ 139.9 ± 0.8, 144.9 ± 1.5, 148.9 ± 1.3 µg/mL, respectively compared to ascorbic acid 14.2 ± 0.5 µg/ml. Moreover TNE, TNC fractions showed more significant cytotoxic activity against HepG-2 with IC₅₀ 82.1 ± 3.1, 101 ± 2.8 µg/mL and MCF-7 with IC₅₀ 114 ± 3.2, 124 ± 3.9 µg/mL respectively. The TNB fraction showed weak cytotoxic activity against both cell lines compared to the other fractions. Ultimately, TNE fraction showed a remarkable anti-obesity activity with IC₅₀ 62.4 ± 1.5 µg/mL compared to chloroform fraction with IC₅₀ 535.6 ± 2.1 µg/mL and n-butanol fraction which did not show any activity. In conclusion, these findings represent the first insights into the phytochemical constituents and pharmacological properties of T. nubica. The ethyl acetate fraction of T. nubica might be a promising source of functional constituents with antioxidant, cytotoxic and anti-obesity potentials. It might be a natural alternative therapy and nutritional strategy, for obesity treatment without dangerous side effects. Isolation of the bioactive compounds from the ethyl acetate fraction of T. nubica and evaluating their biological activities are recommended.     

Polyphenolic characterization and evaluation of multimode antioxidant,cytotoxic, biocompatibility and antimicrobial potential of selected ethno-medicinal plant extracts

IntroductionScientific evidence about biological profile of natural products can support their traditional uses. The current work was aimed to assess phytochemical and biological profile of nine medicinal plants collected from Herbalists.MethodsExtracts prepared in different solvents were subjected to phytochemical, antioxidant, enzyme inhibitory, cytotoxic, and antimicrobial activities. Reverse phase-high performance liquid chromatography (RP-HPLC) analysis was performed for the quantification of polyphenols.ResultsResults showed methanol extract (M) being potent as compared to others. Gentian lutea M showed maximum extract recovery (15.00 ± 0.11 % w/w) and TFC (30.82 ± 0.21 μg QE/mg extract). Nigella sativa M displayed highest TPC (44.99 ± 0.43 μg GAE/mg extract) and TAC (334.72 ± 0.35 μg AAE/ mg extract). Results showed noteworthy quantities of vanillic acid, rutin, kaempferol, emodin in ethyl acetate (EA) and methanol (M) extracts of plants assessed by RP-HPLC. Gentisic acid was highest (11.75 µg/mg extract) in T. arjuna M extract. Similarly, maximum %FRSA (82.28 ± 0.03 %) and TRP (160.40 ± 0.38 μg AAE/ mg extract) were depicted by Terminalia chebula and Chamomilla recutita, respectively. Moreover, Mentha longifolia and G. lutea M demonstrated noteworthy (p < 0.05) antibacterial activity against Staphylococcus aureus (14 ± 0.7 mm) and Klebsiella pneumoniae (12 ± 0.3 mm), respectively. Curcuma amada, C. recutita, Murraya koenigii and G. lutea M had significant α-glucosidase activity. Another good solvent for extraction was ethyl acetate (EA), whose extracts were secondary to methanol in producing significant biological profile. For example, EA of N. sativa (TPC: 1.46 ± 0.45 µg GAE/ mg extract), G. lutea (TRP: 160.33 ± 0.52 μg AAE/mg extract: ZOI of 12 ± 0.5 mm in K. pneumoniae) and Mormodica charantia (α-amylase inhibition: 39.5 ± 0.10 %) showed significant bioactivities. All extracts displayed mild antifungal protein kinase inhibition activities and were significantly (greater than80 %: p < 0.05) cytotoxic to brine shrimps with negligible hemolytic activity.ConclusionBriefly, variable polarity solvent extracts of studied plants will be processed for isolation of antioxidant, cytotoxic, carbohydrate enzyme inhibitory and antibacterial compounds.     

One-pot multicomponent synthesis of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives and their biological evaluation as potential antioxidants,enzyme inhibitors,antimicrobials, cytotoxic and anti-inflammatory agents

A series of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives with substituted amine moieties (1–13) and substituted aldehyde (S) were designed and synthesized by a reflux condensation reaction in the presence of an acid catalyst to get N-Mannich bases. Mannich bases were evaluated pharmacologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cell cytotoxicity and anti-inflammatory activities. Most of the compounds exhibited potent activities against these bioassays. Among them, SH1 and SH13 showed potent antioxidant activity against DPPH free radical at IC₅₀ of 9.94 ± 0.16 µg/mL and 11.68 ± 0.32 µg/mL, respectively. SH7, SH10 and SH13 showed significant results in TAC and TRP antioxidant assays, comparable to that of ascorbic acid. SH2 and SH3 showed potent activity in inhibiting α-amylase enzyme at IC₅₀ of 10.17 ± 0.23 µg/mL and 9.48 ± 0.17 µg/mL, respectively, when compared with acarbose (13.52 ± 0.19 µg/mL). SH7 was the most active against gram-positive and gram-negative bacterial strains, SH13 being the most potent against P. aeruginosa by inhibiting its growth up to 80% (MIC = 11.11 µg/mL). SH4, SH5 and SH6 exhibited significant activity against some fungal strains. Among the thirteen synthesized compounds (SH1-SH13), four were screened out based on the results of brine shrimp lethality assay (LD₅₀) and cell cytotoxicity assay (IC₅₀), to determine their anti-cancer potential against Hep-G2 cells. The study was conducted for 24, 48, and 72 h. SH12 showed potent results at IC₅₀ of 6.48 µM at 72 h when compared with cisplatin (2.56 µM). An in vitro nitric oxide (NO) assay was performed to shortlist compounds for in vivo anti-inflammatory assay. Among shortlisted compounds, SH13 exhibited potent anti-inflammatory activity by decreasing the paw thickness to the maximum compared to the standard, acetylsalicylic acid (ASA).     

Bioinspired synthesis of pure massicot phase lead oxide nanoparticles and assessment of their biocompatibility,cytotoxicity and in-vitro biological properties

Green and ecofriendly route for biosynthesis of lead oxide nanoparticles has been successfully demonstrated using aqueous leaf extracts of Sageretia thea (Osbeck.). Biosynthesized PbO (∼27 nm) nanoparticles were extensively characterized using XRD, FTIR, Raman, EDS etc. Morphology was studied through HR-TEM/SEM. As synthesized nanoparticles were investigated for their iv-vitro biological properties. Antibacterial activities revealed enhancement upon modulation by UV in a concentration dependent manner. Pseudomonas aeruginosa was found to be the most resistant strain (MIC = 250 µg/mL and MIC^uv = 31.25 µg/ml). MTT cytotoxicity on leishmania promastigotes and amastigotes revealed significant inhibition as indicated by their IC₅₀ values of 14.7 µg/mL and 11.95 µg/m respectively. Cytotoxicity was also confirmed using brine shrimp lethality (IC₅₀ = 27.7 µg/mL). Bio-compatibility evaluation indicated cytotoxicity to freshly isolated human macrophages (IC₅₀ = 57.1 µg/mL). Insignificant alpha-amylase inhibition and moderate protein kinase inhibition was revealed. Antioxidant activities indicated free radical scavenging activity (58 ± 2.45) at 200 µg/mL. Moderate total reducing power and total antioxidant activity was also indicated. Overall, we conclude lead oxide as a potential candidate for biological applications, however further studies are recommended on their in vitro and in vivo cytotoxicity.     

UPLC-ESI-QTOF-MS phenolic compounds identification and quantification from ethanolic extract of Myrtus communis ‘Variegatha’: In vitro antioxidant and antidiabetic potentials

Global public health is seriously threatened by diabetes and its complications. Although several synthetic drugs are currently employed for managing diabetes, however, the adverse effects associated with their use cannot be underestimated. Thus, the quest for a safe and cost-effective alternative is highly imperative. In the present study, the phenolic contents, antioxidant, antidiabetic, and cytotoxic potentials of 70% ethanolic crude extract of Myrtus communis ‘Variegatha’ were investigated using in vitro biochemical protocols. The total polyphenols content was 116.44 mg GAE/g, flavonols (6.74 mg QE/g), flavanols (2.46 mg CE/g) and the ferric reducing antioxidant power (FRAP) value was 1267.28 µmol AAE/g, 2,2-diphenyl-1-picrylhydrazyl (DPPH) (1165.37 µmol TE/g), and Trolox equivalent antioxidant capacity (TEAC) (775.52 µmol TE/g). High-resolution ultra-performance liquid chromatography coupled with electrospray ionisation/quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was explored to identify the phenolic compounds, most of which were flavonoids. The extract demonstrated a strong α-glucosidase inhibition potential in a concentration-dependent manner with IC₅₀ (3.159 µg/mL), which was higher than epigallocatechin gallate (EGCG) (6.208 µg/mL), a positive control antidiabetic drug. A slight increase in glucose utilization was observed after 24 h of treatment in C3A hepatocytes at 25 μg/mL whereas an increase in glucose uptake was recorded at 25 and 50 μg/mL. The extract exhibited a cytotoxic effect (IC₅₀ 76.85 µg/mL) against C3A hepatocytes at 100 µg/mL, which correlates to the glucose utilization and uptake recorded. The findings from the study show the prospect of M. communis ‘Variegatha’ as a promising source of bioactive compounds that could be used in the development of new anti-diabetic agents, thus, further research into the plant is recommended.     

Anti-pathogenic,anti-diabetic,anti-inflammatory,antioxidant, and wound healing efficacy of Datura metel L. leaves

Datura metel L. is an important medicinal plant of Solanaceae family which has extensive pharmacological properties. The present investigation was aimed to identify the presence of phytoconstituents and assess in vitro antibacterial, anti-biofilm, anti-diabetic, anti-inflammatory, antioxidant, cytotoxicity, and wound healing efficacy of D. metel leaves extract. Among different solvent extracts, methanolic extract showed higher amount of phenolic (124.61 ± 0.68 mg GAE/g), alkaloid (88.77 ± 1.01 mg AE/g), flavonoids (42.24 ± 0.18 mg QE/g), and tannins contents (38.72 ± 0.51 mg GAE/g). The extract exhibited not only significantly (P < 0.05) different antibacterial activities against pathogens tested but also showed maximum biofilm inhibition of 94, 88, and 92% against B. subtilis, MRSA, and E. coli, respectively. Anti-diabetic assay depicted 22.55 ± 0.62–79.41 ± 1.13% and 24.31 ± 1.47–72.59 ± 0.22% of α-amylase and α-glucosidase inhibition abilities of methanolic extract, respectively at varied concentrations. The methanolic extract showed potential anti-inflammatory effect (P < 0.05) by showing 28.11 ± 0.13, 34.94 ± 1.11, 55.73 ± 0.42, 73.28 ± 0.72, and 92.62 ± 1.33% of inhibition of protein denaturation at different concentrations with an IC₅₀ value of 52.45 µg/mL. The extract revealed significant (P < 0.05) rate of ABTS scavenging, DPPH degradation, and reducing power assay in a concentration dependent manner. The cytotoxicity assay was demonstrated on L929 mouse fibroblast cell line and found > 90% of cell viability in the presence of methanolic extract, thereby indicating its non-toxicity effect. Wound healing assay indicated that methanolic extract at 50 µg/mL closed 100% of wound gap after 24 h with high rate of migration and proliferation. Furthermore, GC–MS chromatogram revealed the presence of several components in methanolic extract, including neophytadiene, hexadecanoic acid, and hentriacontane as principal phytoconstituents. In conclusion, methanolic extract of D. metel leaves could be used as potent therapeutic agent not only for treating metabolic diseases but also superficial chronic diabetic wounds.     

Bioprospecting Dodonaea viscosa Jacq.; a traditional medicinal plant for antioxidant,cytotoxic, antidiabetic and antimicrobial potential

Purpose of studyDodonaea viscosa Jacq. is an ethnomedicinal plant that has been extensively used for the treatment of gout, rheumatism and pain. Current study was undertaken to mine its antioxidant, antimicrobial, cytotoxic and antidiabetic potential. Chromogenic assays were employed to establish plant’s multimode antioxidant profile whereas HPLC fingerprinting was performed to quantify polyphenols. Standard brine shrimp lethality, MTT and SRB assays proved its cytotoxicity potential.ResultsAmong all the extracts (flower, leaf, stem and root), maximum extract recovery (22% w/w), gallic acid equivalent total phenolic content (20.11 ± 0.11 ug GAE/mg DW), ascorbic acid equivalent total antioxidant capacity (22.5 ± 0.07 µg/mg DW) and total reducing power (31.1 ± 1.13 µg/mg DW) were recorded in the distilled water + acetone extract of leaf. The acetone extract of leaf showed maximum quercetin equivalent total flavonoid content (4.78 ± 0.13 µg/mg DW). HPLC-DAD analysis revealed significant amount of rutin, vanillic acid, coumaric acid, ferulic acid, gallic acid, syringic acid, cinnamic acid, gentisic acid, catechin, caffeic acid, apigenin and myricetin in the different plant parts. Maximum scavenging potential was exhibited by methanol + ethyl acetate stem extract (IC₅₀ = 23.8 µg/ml). The highest antibacterial potential was found in flower (85.7%) and root (71.4%) extracts. The ethanol + ethyl acetate (1:1) leaf extract showed noteworthy toxicity against brine shrimps (LC₅₀ = 95.46 µg/ml) while a notable antiproliferative activity against THP-1 (IC₅₀ = 3.4 µg/ml) and Hep G2 (IC₅₀ = 20 µg/ml) cell lines was shown by ethanol + ethyl acetate extracts (1:1) of stem and root, respectively. A moderate inhibition of α-amylase enzyme was observed in all parts of the plant.ConclusionThe results of the present study suggest D. viscosa as a potential source of antioxidant, anticancer and α-amylase inhibitory phytochemicals.     

A Study on the In Vitro Antioxidant Activity of Juniper (Juniperus communis L.) Fruit Extracts

Abstract

This study aimed at evaluating the in vitro antioxidant activity of water and ethanol extracts of juniper (Juniperus communis L., Family Cupressaceae) fruit. The antioxidant properties of both Juniper extracts were studied using different antioxidant assays, including reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. Both the water and the ethanol extracts exhibited strong total antioxidant activity. The concentrations of 20, 40, and 60 µg/mL of water and ethanol extracts of juniper fruit showed 75%, 88%, 93%, 73%, 84%, and 92% inhibition on peroxidation of linoleic acid emulsion, respectively. On the other hand, 60 µg/mL of standard antioxidant such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and α‐tocopherol exhibited 96, 96, and 61 inhibitions on peroxidation of linoleic acid emulsion, respectively. However, both extracts of juniper had effective reducing power, free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities at these same concentrations (20, 40, and 60 µg/mL). Those various antioxidant activities were compared to BHA, BHT, and α‐tocopherol as standard antioxidants. In addition, total phenolic compounds in both aqueous and ethanolic juniper extracts were determined as gallic acid equivalents. Accordingly, these results indicate that juniper has in vitro antioxidant properties and these may be major reasons for the inhibition of lipid peroxidation properties.     

Phytochemical,antioxidant, enzyme inhibitory,thrombolytic, antibacterial,antiviral and in silico studies of Acacia jacquemontii leaves

The main objective of this work was to gain insight into biological propensities, and bioactive phytochemicals of Acacia jacquemontii Benth, a wild plant providing medicinal components, as well as to establish a link between its phytochemical profile and biological activities. Phytochemical profiling revealed the presence of a higher amount of total phenolic (271.44 ± 4.41 mg GAE/g) and flavonoid contents (216.47 ± 5.82 mg QE/g) in methanolic extract (MEAJ), and as compared to n-hexane fraction (HEAJ) and stronger biological activities of MEAJ were possibly linked to the higher bioactive contents. The freshly collected plant leaves showed a strong antioxidant potential (total antioxidant capacity 1.03 ± 0.19 mmol TE/g), which was found even stronger in dried methanolic extract (TAC; 4.36 ± 1.12 mmol TE/g), moreover, MEAJ also showed strong antioxidant potential when investigated by different antioxidant assays (DPPH; 154.04 ± 2.47, ABTS; 122.36 ± 0.80, FRAP; 453.18 ± 5.9, CUPRAC; 1389.97 ± 5.32 mg TE/g). The MEAJ showed good tyrosinase inhibition activity (71.69 %), compared with 83 % inhibition by kojic acid. Ten major compounds identified by GC–MS were docked and eight legends showed lower binding energies (-6 to ?7.8 kcal/mol) compared with kojic acid (-5.9 kcal/mol), which shows the possible role of these compounds in the anti-tyrosinase activity of the extract, and the ADMET analysis predicted the drug-likeness and safety profile of the studied compounds. The thrombolytic effect of MEAJ was 56.41 ± 0.75 to 57.15 ± 1.41 % which was comparable with streptokinase (82.44 ± 1.15 to 84.14 ± 0.95 %). Antibacterial activity of MEAJ was also good (MEAJ; 0.5–2.0 mg/mL, and co-amoxiclav; 5.0–12.5 µg/mL), and the highest activity was observed against Bacillus subtilis (MEAJ; 0.5 mg/mL, co-amoxiclav; 5.0 µg/mL). The antiviral activity of MEAJ was highly strong (HA titer; 00 to 08) against all the tested strains. It can be concluded that A. jacquemontii is a prospective source of phytochemicals with strong biological activities, and their usage in formulations of natural products and pharmaceuticals is recommended, however, further research may address the discovery and development of novel drugs for the pharmaceutical industry.     

Antitubercular and antioxidant activities of hydroxy and chloro substituted chalcone analogues: Synthesis,biological and computational studies

A series of chalcone analogues (1–15) were synthesized by Claisen-Schmidt condensation in good yields (70–95%) and characterized by FT-IR, ¹H NMR and mass spectral methods. Additionally, compounds 3 and 7 were characterized by ¹³C NMR. Antitubercular and antioxidant activities of the chalcones were evaluated by MABA and DPPH free radical assays. In MABA assay analogues 3 (MIC = 14 ± 0.11 µM) and 11 (MIC = 14 ± 0.17 µM) bearing fluorine and methoxy groups at para and meta positions were 1.8-times more active than the standard pyrazinamide (MIC = 25.34 ± 0.22 µM). The chalcone analogues such as compound 7 (IC₅₀ = 4 ± 1 µg/mL) containing electron releasing groups such as OH at ortho position had slightly more antioxidant activity than Gallic acid (IC₅₀ = 5 ± 1 µg/mL). The potential compounds 3, 7, 9 and 11 were less selective and toxic against human live cell lines-LO2. Further, molecular docking results of chalcones against anti-tubercular drug target isocitrate lyase (PDB ID: 1F8M) revealed that compound 3 and 11 shown least binding energies as ?7.6, and ?7.5 kcal/mol are in line with in vitro MABA assay, suggesting that these compounds 3 and 11 are strong inhibitor of isocitrate lyase. SwissADME programme estimated the drug likeliness properties of compounds 3, 7, 9 and 11. The lead molecules arisen through this study helps to develop new antitubercular and antioxidant agents.     

Design,synthesis and biological evaluation of novel quinazoline derivatives as potential NF-κb inhibitors

A series of novel 4-aminoquinazoline derivatives were designed, synthesized and biological properties on nuclear factor-kappaB (NF-κb) pathway inhibitory and potential in vitro anti-proliferation against breast cancer lines were also evaluated. Among them, LU1501 exhibited potent inhibition with IC₅₀ values in SK-BR-3 (10.16 ± 0.86 µM) and HCC1806 (10.66 ± 1.01 µM) cell lines. In vivo studies in breast cancer tumor model proved the correlation between anticancer activity of LU1501 and proliferation inhibition through the NF-κb signal pathway. The molecular docking studies also portrayed the potential binding mechanism between LU1501 and the key proteins of p65 and IkBα in NF-κb pathway. Accordingly, compound LU1501 could serve as a potent agent against breast cancer for further investigation.