In Vitro Antibacterial, DPPH Radical Scavenging Activities, and In Silico Molecular Modeling of Isolated Compounds from the Roots of Clematis hirsuta.

Clematis hirsuta is one of the traditional medicinal plants used in Ethiopia to treat different ailments, such as cancer and diseases related to the respiratory system. This study aimed to isolate the phytochemical components of the root of C. hirsuta and evaluate their in vitro and in silico biological activities. Oleic acid (1), palmitic acid (2), sterols (3 and 4), boehmenan (5), and carolignans E (6 and 7) were isolated by silica gel column chromatography and preparative thin layer chromatography and characterized by NMR spectroscopy. Compounds 5-7 were isolated from the plant for the first time. At 5 mg/mL, the inhibition zone of evaluated compounds ranged from 8.80 to 11.10 mm against all selected bacteria. The MIC of the MeOH and n-hexane: EtOAc (1 : 1) extracts was greater than or equal to 50 mg/mL against all selected bacteria. At 62.5 µg/mL, the % DPPH radical scavenging activity of tested compounds ranged from 30.3% to 92.1% with an IC50 value of 19.4 to 2.1 µg/mL. The results of molecular docking studies indicated that the docking scores of compounds 3-7 ranged from -6.4 to -7.9 kcal/mol against E. coli DNA gyrase B, -8.3 to -9.0 kcal/mol against the Pseudomonas quinolone signal A, -7.1 to -8.5 kcal/mol against pyruvate kinase M2, and -7.9 to -8.5 kcal/mol against human topoisomerase IIß. The results of the in silico antibacterial activity of compounds 3, 5, and 6 supported the in vitro antibacterial test results. Compound 5 had a better docking score against human topoisomerase IIß than the other test samples demonstrating its potential as an anticancer agent. Therefore, compounds 3-7 could be considered as a lead for developing antibacterial and anticancer drugs. Moreover, the presence of these active phytochemicals supports the traditional use of this plant against cancer and bacteria.

Antibacterial and Antioxidant Efficacies of Secondary Metabolites from the Roots of Cyphostemma adenocaule: A Combined In Vitro and In Silico Study.

Cyphostemma adenocaule is a therapeutic plant traditionally used to treat rabies, snake bite, diarrhea, and wound healing. To address the bioactive compounds exhibiting these activities, we performed a comprehensive study on the roots of the plant. Thus, the present study aims to inspect the in vitro antioxidant and antibacterial efficacies of compounds isolated from the combined dichloromethane : methanol (1 : 1) and methanol extracts of C. adenocaule along with the in silico study of their interaction with selected protein targets. The silica gel column chromatography technique was used for the isolation of compounds, and the antibacterial and antioxidant activities were evaluated using agar disc diffusion and DPPH radical scavenging assays, respectively. Furthermore, in silico molecular docking screening, pharmacokinetics, and toxicity protocols of the compound isolates were performed to offer the potential applications of the compounds in developing novel medications. A BIOVIA Discovery Studio in combination with AutoDock Vina 4.2 software, SwissADME, and ProTox-II prediction web tools were used to generate the molecular docking, pharmacokinetics, and toxicity profiles, respectively. Notably, the chromatographic separation of the combined extracts yielded six known compounds, namely, ß-sitosterol (1), 3-hydroxyisoagatholactone (2), ε-viniferin (3), myricetin (4), tricuspidatol A (5), and parthenocissin A (6). The in vitro antibacterial activities revealed the highest inhibition zone by tricuspidatol A (5) (16.67 ± 0.47), showcasing its potent activity against S. aureus at 2 mg/mL, compared to ciprofloxacin (21.50 ± 0.41). ε-Viniferin (3) (IC50: 0.32 µg/mL) exhibited greater antioxidant activity than the others and displayed promising results compared to ascorbic acid (0.075 µg/mL). The molecular docking study revealed the highest binding affinity by ε-viniferin (3) (-9.9 kcal/mol) against topoisomerase II α. 3-Hydroxyisoagatholactone (2) and ε-viniferin (3) fulfilled Lipinski's rule with no violation, and the organ toxicity predictions revealed that all the compounds showed no cytotoxicity and hepatotoxicity effects. Thus, this study's combined in vitro and in silico outcomes suggest the potential use of the isolated compounds in drug discovery and support the traditional relevance of C. adenocaule.

In vitro antimicrobial and antioxidant activities, essential oil composition, and in silico molecular modeling analysis of secondary metabolites from roots of Verbascum sinaiticum.

Verbascum sinaiticum is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from V. sinaiticum. The 1H-NMR, 13C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3'-(4''-methoxy phenyl)-3'-oxo-propionyl hexadecanoate (1), harpagoside (2), pulverulentoside I (3), scrophuloside B4 (4), scropolioside A (5), scropolioside-D2 (6), and harpagide 6-O-ß-glucoside (7), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to Streptococcus agalactiae, with a 2 mg/mL MIC. The EO from roots was effective against Candida albicans and Trichophyton mentagrophytes, with a MIC of 8 mg/mL. The MeOH and CH2Cl2/CH3OH (1:1) root extracts showed the maximum activity against S. epidermidis with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against Staphylococcus epidermidis, which exhibited a 0.0625 mg/mL MIC for compound 1. The strongest radical scavenging activity was exhibited by the methanol extract (IC50 = 3.4 µg/mL), and compounds 4, 6, 5, 3, 7, and 2 with IC50 values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 µg/mL, respectively, in comparison with ascorbic acid (IC50 = 1.3 µg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from -38.5 to -43.1 kJ/mol, -33.1 to -42.7 kJ/mol, -34.7 to -39.3.7 kJ/mol, -25.5 to -37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase IIß (PDB ID: 4fm9), S. epidermidis FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the in vitro antibacterial activity are in good agreement. These findings show that the isolated compounds 2-7 can act as potential antioxidants and strong antibacterials against Staphylococcus aureus and S. epidermidis. As a result, V. sinaiticum root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plant's potential candidate.

In Silico Molecular Docking Analysis, Cytotoxicity, and Antibacterial Activities of Constituents of Fruits of Cucumis dipsaceus.

Cucumis dipsaceus (Cucurbitaceae) is a plant traditionally used against diarrhea, teeth-ach, wounds, stomach ache, meningitis, and cancer. The extracts of C. dipsaceus after silica gel column chromatography gave nine compounds identified using spectroscopic methods such as hexacosane (1), octadecane (2), 17-(-5-ethyl-2,6-dihydroxy-6-methylhept-3-en-2-yl)-9-(hydroxymethyl)-13-methylcyclopenta[α]phenanthren-3-ol (3), erythrodiol (4), (9,12)-propyl icosa-9,12-dienoate (5), α-spinasterol (6), 16-dehydroxycucurbitacin (7), cucurbitacin D (8), and 23,24-dihydroisocucurbitacin D (9). Compounds 3 and 4 are new to the genus Cucumis. α-Spinasterol showed better inhibition zone diameter = 13.67 ± 0.57, 15.00 ± 0.10, and 13.33 ± 0.57 mm against Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes compared with the other tested samples. α-Spinasterol (-8.0 kcal/mol) and 3 (-7.6 kcal/mol) displayed high binding affinity against DNA Gyrase compared to ciprofloxacin (-7.3 kcal/mol). α-Spinasterol and 16-dehydroxycucurbitacin showed better binding affinity against protein kinase. The cytotoxicity results revealed that the EtOAc extract showed the highest potency with IC50 = 16.05 µg/mL. 16-Dehydroxycucurbitacin showed a higher binding affinity (-7.7 kcal/mol) against human topoisomerase IIß than etoposide. The cytotoxicity and antibacterial activities and in silico molecular docking analysis displayed by the constituents corroborate the traditional use of the plant against bacteria and cancer.

Isolation and identification of endophytic bacteria and associated compound from Gloriosa superba and their antibacterial activities.

Gloriosa superba L., which belongs to the genus Gloriosa and family Colchicaceae, is a climbing annual herb and tuberous poisonous tropical medicinal plant. This study was aimed to isolate possible endophytic bacteria from leaves, stems and tubers of Gloriosa superba. Thirty pure endophytic bacteria were isolated and subjected to biochemical characterization. Bacterial identification was conducted by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The structure of the isolated compound was characterized. The antibacterial activity was also evaluated. Majority (21, 70 %) of the isolates were Gram-positive. Certain of them are spore formers. Based on MALDI-TOF MS, 26 of the isolates were identified as Bacillus spp. (65.4 %), Escherichia spp. (30.8 %) and Providencia spp. (3.9 %). A 1-undecene was isolated from culture filtrate of E. coli (GST-5). The ethyl acetate extracts (1000 µg/mL) of GSL-5 and GST-2 culture filtrates recorded maximum inhibition zone against E. coli (9.4 ± 0.6 mm) and S. aurous ATCC 25923T (8.4 ± 0.8 mm), respectively. The Pseudomonas aeruginosa ATCC 27853T was prone to all ethyl acetate extracts. A 1-undecene showed a moderate activity against E. coli ATCC 25922Tand P. aeruginosa ATCC 27853T at 50 µg/mL. The present finding would be a breakthrough to studies of similar works in Ethiopia since it may be for the first time.

Ultrasonic-Assisted Synthesis of Heterocyclic Curcumin Analogs as Antidiabetic, Antibacterial, and Antioxidant Agents Combined with in vitro and in silico Studies.

Background: Heterocyclic analogs of curcumin have a wide range of therapeutic potential and the ability to control the activity of a variety of metabolic enzymes. Methods: 1H-NMR and 13C-NMR spectroscopic techniques were used to determine the structures of synthesized compounds. The agar disc diffusion method and α-amylase inhibition assay were used to examine the antibacterial and anti-diabetic potential of the compounds against α-amylase enzyme inhibitory activity, respectively. DPPH-free radical scavenging and lipid peroxidation inhibition assays were used to assess the in vitro antioxidant potential. Results and Discussion: In this work, nine heterocyclic analogs derived from curcumin precursors under ultrasonic irradiation were synthesized in excellent yields (81.4-93.7%) with improved reaction time. Results of antibacterial activities revealed that compounds 8, and 11 displayed mean inhibition zone of 13.00±0.57, and 19.66±00 mm, respectively, compared to amoxicillin (12.87±1.41 mm) at 500 µg/mL against E. coli, while compounds 8, 11 and 16 displayed mean inhibition zone of 17.67±0.57, 14.33±0.57 and 23.33±00 mm, respectively, compared to amoxicillin (13.75±1.83 mm) at 500 µg/mL against P. aeruginosa. Compound 11 displayed a mean inhibition zone of 11.33±0.57 mm compared to amoxicillin (10.75±1.83 mm) at 500 µg/mL against S. aureus. Compound 11 displayed higher binding affinities of -7.5 and -8.3 Kcal/mol with penicillin-binding proteins (PBPs) and ß-lactamases producing bacterial strains, compared to amoxicillin (-7.2 and -7.9 Kcal/mol, respectively), these results are in good agreement with the in vitro antibacterial activities. In vitro antidiabetic potential on α-amylase enzyme revealed that compounds 11 (IC50=7.59 µg/mL) and 16 (IC50=4.08 µg/mL) have higher inhibitory activities than acarbose (IC50=8.0 µg/mL). Compound 8 showed promising antioxidant inhibition efficacy of DPPH (IC50 = 2.44 g/mL) compared to ascorbic acid (IC50=1.24 g/mL), while compound 16 revealed 89.9±20.42% inhibition of peroxide generation showing its potential in reducing the development of lipid peroxides. In silico molecular docking analysis, results are in good agreement with in vitro biological activity. In silico ADMET profiles suggested the adequate oral drug-likeness potential of the compounds without adverse effects. Conclusion: According to our findings, both biological activities and in silico computational studies results demonstrated that compounds 8, 11, and 16 are promising α-amylase inhibitors and antibacterial agents against E. coli, P. aeruginosa, and S. aureus, whereas compound 8 was found to be a promising antioxidant agent.

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review.

The incorporation of heterocyclic moieties into the standard chemical structure with a biologically active scaffold has become of crucial practice for the construction of pharmacologically potent candidates in the drug arena. Currently, numerous kinds of chalcones and their derivatives have been synthesized using the incorporation of heterocyclic scaffolds, especially chalcones bearing heterocyclic moieties that display improved efficiency and potential for drug production in pharmaceutical sectors. The current Review focuses on recent advances in the synthetic approaches and pharmacological activities such as antibacterial, antifungal, antitubercular, antioxidant, antimalarial, anticancer, anti-inflammatory, antigiardial, and antifilarial activities of chalcone derivatives incorporating N-heterocyclic moieties at either the A-ring or B-ring.

Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review.

4-Quinolone and its analogs are heterocyclic classes of organic compounds displaying biologically active and a broad spectrum of pharmaceutical drug scaffolds. 4-Quinolone is the first-line chemotherapeutic treatment for a wide spectrum of bacterial infections. Recently, 4-quinolone and its derivatives have been shown to have the potential to cure and regulate various acute and chronic diseases, including pain, ischemia, immunomodulation, inflammation, malarial, bacterial infection, fungal infection, HIV, and cancer, based on several reports. This review highlights and provides brief information to better understand the development of experimental progress made to date in the synthetic protocol towards 4-quinolone and its analogs. Thus, classical synthesis protocol, metal-free reaction protocol, and transition metal-catalyzed reaction procedures are briefly discussed along with the pharmaceutical activities of selected 4-quinolone derivatives.

Furoquinoline and bisindole alkaloids from the roots of Teclea nobilis and their in-silico molecular docking analysis.

Teclea nobilis is a medicinal plant widely used to treat oral pathogens, gonorrhea, fever, analgesics, asthma, joint pains, pneumonia, and intestinal worms in Ethiopia. Anticipated by these claims, column chromatographic separation of the roots extract of T. nobilis led to the isolation of eight alkaloids (1-8). The structures of the isolated compounds were identified based on their NMR (1D and 2D) spectral data analysis and comparison with reported literature data. In-silico molecular docking analysis of the isolated compounds were performed against Staphylococcus aureus DNA Gyrase (PDB ID: 2XCT) and human topoisomerase IIß DNA (PDB ID: 3QX3) by using AutoDock Vina. ADMET analysis were performed by SwissADME, PreADMET, and OSIRIS Property predictions. The study revealed that the isolated compounds exhibited promising binding affinity to DNA gyrase, especially with compound 5 forms a stable drug-protein complex. Whereas the ADME and drug-likeness analysis revealed that compound 5 is less absorbed from the gastrointestinal tract, crossblood brain barrier and a P-glycoprotein substrate. This indicated that compound 5 could be a good candidate as anticancer agent provided that in vivo analysis done for more confirmation.

Compounds with antibacterial and antioxidant activities from Cadia purpurea.

Five compounds 1-5 were reported from leaves and roots of Cadia purpurea herein. 2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-17-(1-hydroxypent-4-en-2-yl)-10,13-dimethyl-1H-cyclopenta[a]phenanthren-3-ol (1), apigenin-7-O-rhaminoglucoside (2) and 13-O-pyrrolecarboxyl lupanine (3) were isolated from chloroform and methanol leaves extracts. And 5-((trihydro-2-oxy-4-(hydroxymethyl)-5-(3-hydroxyphenyl)furan-3yl)methyl)benzene-1,2,3,4-tetraol (4) and bis(2-hydroxybutyl) phthalate (5) were isolated from the chloroform: methanol (1:1) roots extract. The structures of the compounds were characterized using NMR, IR and GC/MS spectroscopic data. In vitro antibacterial and antioxidant activities of leaves extracts and compounds 1, 2, 4, and 5 were also evaluated. The present findings disclosed that tested compound isolates and extracts showed dose-dependent antibacterial and antioxidant activities. The molecular docking result indicates that isolated compounds show no violation of the Lipinski's rule of five. Compounds 1, 2, 4, and 5 were reported herein for the first time from the leaves and roots of C. purpurea. Further biochemical investigation on whole parts of the plant may uncover additional chemical entities with better biological activities.

Synthesis, antiplasmodial activity and in silico molecular docking study of pinocembrin and its analogs.

BACKGROUND: Malaria remains the major health problem responsible for many mortality and morbidity in developing countries. Because of the development of resistance by Plasmodium species, searching effective antimalarial agents becomes increasingly important. Pinocembrin is a flavanone previously isolated as the most active antiplasmodial compound from the leaves of Dodonaea angustifolia. For a better understanding of the antiplasmodial activity, the synthesis of pinocembrin and a great number of analogs was undertaken. METHODS: Chalcones 5a-r were synthesized via Claisen-Schmidt condensation using 2,4-dibenzyloxy-6-hydroxyacetophenone and aromatic aldehydes as substrates under basic conditions. Cyclization of compounds 5a-r to the corresponding dibenzylated pinocembrin analogs 6a-r was achieved using NaOAc in EtOH under reflux. Catalytic hydrogenation using 10% Pd/C as catalyst in an H-Cube Pro was used for debenzylation to deliver 7a-l. The structures of the synthesized compounds were characterized using various physical and spectroscopic methods, including mp, UV, IR, NMR, MS and HRMS. The synthesized dibenzylated flavanones 6a-d, 6i and 7a were evaluated for their in vivo antiplasmodial activities against Plasmodium berghei infected mice. Molecular docking simulation and drug likeness properties of compounds 7a-l were assessed using AutoDock Vina and SwissADME, respectively. RESULTS: A series of chalcones 5a-r has been synthesized in yields ranging from 46 to 98%. Treatment of the chalcones 5a-r with NaOAc refluxing in EtOH afforded the dibenzylated pinocembrin analogs 6a-r with yields up to 54%. Deprotection of the dibenzylated pinocembrin analogs delivered the products 7a-l in yields ranging from 78 to 94%. The dibenzylated analogs of pinocembrin displayed percent inhibition of parastaemia in the range between 17.4 and 87.2% at 30 mg/kg body weight. The parastaemia inhibition of 87.2 and 55.6% was obtained on treatment of the infected mice with pinocembrin (7a) and 4'-chloro-5,7-dibenzylpinocembrin (6e), respectively. The mean survival times of those infected mice treated with these two compounds were beyond 14 days indicating that the samples suppressed P. berghei and reduced the overall pathogenic effect of the parasite. The molecular docking analysis of the chloro derivatives of pinocembrin revealed that compounds 7a-l show docking affinities ranging from - 8.1 to - 8.4 kcal/mol while it was -7.2 kcal/mol for chloroquine. CONCLUSION: Pinocembrin (7a) and 4'-chloro-5,7-dibenzyloxyflavanone (6e) displayed good antiplasmodial activity. The in silico docking simulation against P. falciparum dihydrofolate reductase-thymidylate synthase revealed that pinocembrin (7a) and its chloro analogs 7a-l showed better binding affinity compared with chloroquine that was used as a standard drug. This is in agreement with the drug-like properties of compounds 7a-l which fulfill Lipinski's rule of five with zero violations. Therefore, pinocembrin and its chloro analogs could serve as lead compounds for further antiplasmodial drug development.

In Vitro Antibacterial and Antioxidant Activities and Molecular Docking Analysis of Phytochemicals from Cadia purpurea Roots.

Phytochemicals and antibacterial and antioxidant activities of Cadia purpurea roots were investigated herein for the first time. The phytochemical study led to the isolation of two compounds, di-(2-methylheptyl) phthalate (1) and 13-O-pyrrolecarboxyl lupanine (2), from methanol roots extract of C. purpurea. The antibacterial activity results revealed that the n-hexane extract presented a better inhibitory value (13.8 ± 0.0 mm) followed by chloroform (11.1 ± 0.4 mm) and chloroform : methanol (1 : 1) (10.7 ± 0.1 mm) extracts against E. coli at the maximum dose of 100 mg/mL. While, methanolic and ethanolic extracts displayed a mild activity against same bacterium at same dose. The methicillin resistant S. aureus was found with almost total resistance to all extracts up to the 100 mg/mL. The chloroform : methanol (1 : 1), chloroform, and n-hexane extracts recorded inhibition zone values (8.0 ± 0.0-10.0 ± 0.1 mm, 7.7 ± 0.0-9.8 ± 0.1 mm, and 7.3 ± 0.2-8.9 ± 0.2 mm, respectively) better than chloramphenicol (7.2 ± 0.6 mm at 30 µg dose) against P. aeruginosa. The alcoholic extracts also exhibited an activity better than chloramphenicol up to 25 mg/mL against same bacterium. Compound 2 produced a comparable inhibition value (9.6 ± 0.0 mm to 18.5 ± 0.0 mm) to that of chloramphenicol (21.5 ± 0.3 mm) against E. coli at doses up to 1.0 mg/mL; whereas, compound 1 showed a slight activity (7.1 ± 0.1 mm-10.3 ± 0.0 mm). Both compounds were found generally inactive against S. aureus, while they provided an activity better than chloramphenicol (7.2 ± 0.6 mm) against P. aeruginosa with inhibition zones ranging from 7.1 ± 0.0 mm to 9.0 ± 0.1 mm for compound 1 and 7.2 ± 0.0 mm to 10.6 ± 0.0 mm for compound 2. Ethanolic and methanolic extracts exhibited a better DPPH radical scavenging activity (IC50 values of 12.9 and 16.03 µg/mL, respectively) and strong ferric ion reducing power (with absorbance of 0.788 ± 0.000 and 0.810 ± 0.001, respectively) at a concentration of 500 µg/mL compared to the other extracts. Compound 1 also possessed a better anti-DPPH trapping activity (IC50, 7.99 µg/mL) than compound 2 (IC50, 58.34 µg/mL). The compounds, however, indicated a weak ferric ion reduction power even at higher amount. In general, the observed antibacterial and antioxidant activities of isolated compounds and extracts were found to be dose-dependent. Conducting further biochemical investigations on all parts of this plant could provide opportunities of finding extra alkaloidal compounds and other phthalate derivatives with better biological activity.

Synthesis, in silico molecular docking analysis, pharmacokinetic properties and evaluation of antibacterial and antioxidant activities of fluoroquinolines.

BACKGROUND: Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs. METHODS: 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier-Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina against E. coli DNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET. RESULTS: Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds 4, 5, 6, 7, 8, 10, 15, and 16 exhibited activity against E. coli, P. aeruginosa, S. aureus and S. pyogenes with IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 µg/mL. Compound 9 displayed IZ against three of the bacterial strains except S. aureus. The IC50 for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 µg/mL. The binding affinities of the synthesized compounds were from - 6.1 to - 7.2 kcal/mol against E. coli DNA gyrase B and - 6.8 to - 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski's rule of five without violation. CONCLUSION: Compounds 4, 5, 6, 7, 8, 10, 15, and 16 displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound 8 (13.6 ± 0.22 mm) showed better IZ against P. aeruginosa compared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds 5, 6, 7, 8, 9 and 10 showed comparable binding affinities in their in silico molecular docking analysis against E. coli DNA gyrase B. All of the synthesized compounds also obeyed Lipinski's rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds 7 and 8 were proved to be a very potent radical scavenger with IC50 values of 5.31 and 5.41 µg/mL, respectively. Compound 5, 6, 8, 10 and 16 had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.

Antibacterial, Docking, DFT and ADMET Properties Evaluation of Chalcone-Sulfonamide Derivatives Prepared Using ZnO Nanoparticle Catalysis.

INTRODUCTION: In the present work, two novel compounds were synthesized using zinc oxide nanoparticles through green synthesis protocol. The zinc oxide nanoparticles catalyzed reactions were afforded good to excellent yields of the target compounds 76.3-98.6%. METHODOLOGY: The synthesized compounds were characterized by UV-Vis, IR and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Salmonella typhimurium). RESULTS AND DISCUSSION: The synthesized compounds displayed potent activity against the bacterial strains. Among them, compound 8 showed strong activity against Bacillus cereus relative to the standard drug. On the other hand, compound 9 exhibited strong activity against Escherichia coli. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase and E. coli dihydropteroate synthase and all of them were found to have minimum binding energy ranging from -6.0 to -7.3 kcal/mol, and the best result achieved with compound 8 and 9. CONCLUSION: The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as a lead compound.

Antibacterial and antioxidant activities of extracts and isolated compounds from the roots extract of Cucumis prophetarum and in silico study on DNA gyrase and human peroxiredoxin 5.

BACKGROUND: Cucumis prophetarum is traditionally used to treat liver and lung disorders, heart failure, diarrhea, gonorrhea, skin infections, intestinal problems and cancer. In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time. METHODS: Silica gel column chromatography was applied to separate constituents of the roots of C. prophetarum. The structures of isolated compounds were established using 1H NMR, 13C NMR, DEPT-135, COSY, HSQC and HMBC. Agar well diffusion, DPPH assay and ferric thiocyante methods were used for antibacterial, radical scavenging and anti-lipid peroxidation activities, respectively. AutoDock Vina open source program was used for molecular docking analysis. RESULTS: Evaluation of the in vitro antibacterial activity of the constituents against S. aureus, B. subtilis, E. coli and S. thyphimurium revealed that the hexane extract were active against E. coli with IZ of 15.0 ± 1.41 mm, whereas an IZ of 14.6 ± 1.70 mm for MeOH extract was observed against S. aureus. Compound 1 displayed IZ of 13.6 ± 0.94 mm against E. coli and curcurbiatin 2 showed activity against B. subtilis with IZ of 13.3 ± 0.54 mm. The molecular docking analysis showed that cucurbitacins 2 and 3 have binding energy of -6.7 and -6.9 kcal/mol, respectively. The methanol and the hexane extracts of the roots of C. prophetarum inhibited DPPH radical by 70.4 and 63.3% at 100 µg/mL, respectively. On the other hand, the methanol extract inhibited lipid peroxidation by 53.0%. CONCLUSION: The present study identified five compounds from the root extracts of C. prophetarum, of which two are novel cucurbitacins (1, 2). The in vitro antibacterial activity of the hexane and methanol extracts was better than the activity displayed by the isolated compounds. This is probably due to the synergistic effects of the constituents present in the root extract. The in silico molecular docking study results showed that, compounds 2 and 3 have minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of DNA gyrase B. Furthermore, the "drug-likeness" and ADMET prediction of compounds 2-5 nearly showed compliance with the Lipinski rule, with good absorption, distribution, metabolism, and excretion generally. The radical scavenging and anti-lipid peroxidation activities of the extracts were better than the isolated compounds. This is attributed to the presence of phenolics and flavonoids as minor constituents in the extracts of these species. Therefore, the in vitro antibacterial activity and molecular docking analysis suggest the potential use of the isolated compounds as medicine which corroborates the traditional use of the roots of C. prophetarum.

Molecular docking analysis and evaluation of the antibacterial and antioxidant activities of the constituents of Ocimum cufodontii.

Ocimum cufodontii ((Lanza) A.J.Paton) has been traditionally used in Ethiopia against bacteria. The extracts of the leaves and roots of O. cufodontii after silica gel column chromatography furnished compounds 1-5, compounds 3 and 4 are new natural products. The oil from the hydro-distillation of the leaves, after analyzed with GC-MS, has led to the identification of ß-caryophyllene as a principal component, suggesting the essential oil as medicine and spices to enhance the taste of food. The constituents of O. cufodontii were assessed for their antibacterial activity against E. coli, K. pneumonia, S. typhymurium and S. aureus. The best activity was displayed against S. aureus by the hexane extract of the roots, compound 4, and the essential oil with an inhibition zone of 17, 15, and 19 mm, respectively. Molecular docking analysis revealed that compound 1 has better docking efficiency and forms hydrophobic interactions with five amino acids (ARG192, PHE196, GLU185, GLU193, and LYS189). This suggests that the compounds may act as potential inhibitors of DNA gyrase. The constituents were also assessed for their antioxidant activities using DPPH, ferric thicyanate and ferric reducing power assay. The hexane extracts of the roots inhibited the DPPH radical and peroxide formation by 90.5 and 83%, respectively, suggesting the potential of the extract as an antioxidant. Furthermore, the hexane extract of the roots of O. cufodontii exhibited the maximum reducing power compared with the EtOAc and methanol extracts. Hence, the activity displayed herein indicated as the plant has great potential as a remedy for diseases caused by bacteria and radicals.

Synthesis, Molecular Docking Analysis, and Evaluation of Antibacterial and Antioxidant Properties of Stilbenes and Pinacol of Quinolines.

Emergence of antimicrobial resistance to standard commercial drugs has become a critical public health concern worldwide. Hence, novel antimicrobials with improved biological activities are urgently needed. In this regard, a series of quinoline-stilbene derivatives were synthesized from substituted quinoline and benzyltriphenylphosphonium chloride using Wittig reaction. Furthermore, a novel pinacol of quinoline was synthesized by pinacolinazation of 2-methoxyquinoline-3-carbaldehyde which was achieved by aluminum powder-potassium hydroxide reagent combination at ambient temperature in methanol. The structures of the synthesized compounds were established based on their spectral data. The antibacterial activities of the synthesized compounds were evaluated in vitro by the paper disc diffusion method against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli and Salmonella typhimurium). The best activity was displayed by compound 19 against E. coli with an inhibition zone of 16.0 ± 0.82 mm and 14.67 ± 0.94 mm at 500 and 250 µg/mL, respectively. This is close to ciprofloxacin which is used as a positive control. The results of in silico molecular docking evaluation of the compounds against E. coli DNA gyraseB were in good agreement with the in vitro antibacterial analysis. Compounds 19 (-6.9 kcal/mol) and 24 (-7.1 kcal/mol) showed the maximum binding affinity close to ciprofloxacin (-7.3 kcal/mol) used as positive control. Therefore, the antibacterial activity displayed by these compounds is encouraging for further investigation to improve the activities of quinoline-stilbenes by incorporating various bioisosteric groups in one or more positions of the phenyl nuclei for their potential pharmacological use. Findings of the DPPH radical scavenging assay indicated that some of the quinolone stilbenes and pinacol possess moderate antioxidant properties compared to ascorbic acid used as a natural antioxidant.

Chemical Constituents of Root Barks of Gnidia involucrata and Evaluation for Antibacterial and Antioxidant Activities.

The genus Gnidia, with species close to 152, is traditionally used to treat wide ranges of ailments in humans and animals. Gnidia involucrata is one of the species found in Ethiopia and traditionally used as a laxative, antirheumatic agent, insecticide, antibacterial agent, and antimalarial agent. In view of its traditional use, the root bark was sequentially extracted with n-hexane, EtOAc, and MeOH to afford 0.78%, 4%, and 6% crude extracts, respectively. The chromatographic separation of the EtOAc extract using silica gel column chromatography yielded three pure compounds: tetratriacontanyl caffeate (1), 12-O-dodeca-2,4-dienoylphorbol-13-acetate (2), and naringenin (3). This is the first report of the isolation of 1 and its kind from the genus and most probably from the Thymelaeaceae family. The structures of these compounds were characterized and identified by NMR and mass spectrometric analyses and comparison with literature data. The EtOAc extract and isolated compounds were assessed for their in vitro antibacterial and antioxidant activities. The EtOAc extract (1.5 mg/mL) showed significant inhibitory activity against S. aureus, E. coli, P. mirabilis, and K. pneumonia bacterial strains with the highest inhibition zone observed against S. aureus (23 mm), which is even greater than that of the reference drug ciprofloxacin (22 mm). However, the inhibition displayed on these bacterial strains for the three pure compounds was marginal with variable degrees of potency between the compounds. The better activity of the crude extract could be due to the synergistic interactions of several phytochemicals present in the extract, which cannot be the case when pure compounds are evaluated alone. The antioxidant activities of the extracts and isolated compounds were evaluated using DPPH and ferric thiocyanate methods. The EtOAc and MeOH extracts and compounds 1 and 2 were found to inhibit the DPPH radical by 70.7, 66.9, 85.8, and 52.8%, respectively. The EtOAc extract and compound 1 inhibited peroxidation of lipids by 84 and 86%, respectively. The radical scavenging displayed by compound 1 was significant compared with that displayed by ascorbic acid, indicating the strong antilipid peroxidation potential of the extract of root barks of G. involucrata. Therefore, the extracts of the root bark of G. involucrata can be used as a remedy in combating diseases caused by bacteria and free radicals provided that further comprehensive evaluation could be recommended for the conclusive decision on potential candidacy of this plant.

Antibacterial Activity of Two Flavans from the Stem Bark of Embelia schimperi.

Embelia schemperi Vatke is one of the medicinal plants used traditionally for treatment of intestinal tape worm, dysmenorrheal, bacterial, and fungal infections. Phytochemical screening test of the dichloromethane/methanol (1 : 1) and methanol extracts revealed the presence of phenols, alkaloids, tannins, and flavonoids whereas terpenoids, glycoside, and phytosterols were absent. Silica gel column chromatographic separation of the methanol extract afforded 3,5,7,3',4'-pentahydroxyflavan, named epicatechin (1), along with a close flavan derivative (2). Structures of the compounds were elucidated by spectroscopic techniques (1D and 2D NMR, FTIR, and UV-Vis). The crude extracts and isolated compounds were screened for in vitro antibacterial activity against strains of Klebsiella pneumoniae, Escherichia coli, Cryptococcus neoformans, Shigella dysentriae, and Staphylococcus aureus. Epicatechin (1) exhibited comparable antibacterial activity against S. aureus and E. coli (15 and 12 mm zone of inhibition, resp.) to that of the control antibiotic gentamicin, with zone of inhibition of 15 and 12 mm, respectively, at a concentration of 20 µg/mL.

Antibacterial and Antioxidant Compounds from the Flower Extracts of Vernonia amygdalina.

Vernonia amygdalina is traditionally used in Ethiopia to treat various diseases. This prompted us to isolate bioactive compounds from the flowers of this plant. The CHCl3 extract after silica gel column chromatography has led to the isolation of two compounds identified as tricosane (1) and vernolide (2), while the acetone extract furnished isorhamnetin (3) and luteolin (4). The acetone extract and isorhamnetin significantly scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by 91.6 and 94%, respectively. It was also shown that the acetone extract and isorhamnetin inhibited lipid peroxidation by 74 and 80%, respectively. The extracts and isolated compounds were also evaluated for their antibacterial activity with the CHCl3 extract and vernolide showing strong activity against S. aureus with an inhibition zone of 21 and 19 mm, respectively. On the other hand, the acetone extract and isorhamnetin were active against all bacterial pathogens tested. The work presented herein has demonstrated that vernolide and isorhamnetin had antibacterial activity. The antioxidant activity displayed by the flowers of V. amygdalina is accounted to the presence of isorhamnetin. Therefore, the biological activities displayed by the extracts and isolated compounds from this plant corroborate the traditional uses of this plant by the local people against various diseases.