Background: Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds.Results: Among the synthesized compounds,11showed good activities towards Gram-negativeE. coli(14.40 ± 0.04), and Gram-positiveS. aureus(15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds7and9displayed better DPPH radical scavenging potency with IC₅₀values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within − 7.5 to − 6.0 kcal/mol, compared to amoxicillin (− 6.1 kcal/mol). The highest binding affinity was achieved for compounds9and11(− 6.9, and − 7.5 kcal/mol, respectively). Compounds7and9displayed the binding affinity values of − 5.3 to − 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (− 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD₅₀) value are class three (50 ≤ LD₅₀ ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities.Conclusions: The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11is a promising antibacterial therapeutics agent againstE. coli,whereas compounds7and9were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method.

Background: Uvaria scheffleri (Annonaceae), Clematis burgensis (Ranunculaceae), and Euphorbia schimperiana (Euphorbiaceae) are medicinal plants traditionally used to treat cough, tuberculosis, asthma, sore throat and skin infections. Methods: Silica gel column chromatographic separation was used to isolate compounds. Crude extract and isolated compounds were evaluated for antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans via the broth dilution method. Docking studies were performed with E. coli DNA-Gyrase B and human DNA topoisomerase IIα by using AutoDock Vina. ADMET were predicted by SwissADME, PreADMET, and OSIRIS Property predictions. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels. Results: Silica gel column chromatographic separation afforded five compounds 1– 5 of which N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol ( 1) is reported herein for the first time, along with known C-benzylated dihydrochalcone uvaretin ( 2), bis(2-ethylheptyl) phthalate ( 3), lupeol ( 4) and suberosin derivative ( 5). Dichloromethane roots extract of U. scheffleri showed potent antibacterial activity against S. aureus (MIC = 6.25 μg/mL) compared to gentamicin (MIC=5 μg/mL). In silico, molecular docking analysis of compounds ( 1and 3– 5) showed strong interaction with E. coli DNA gyrase B with a binding energy value ranging from − 6.9 to − 6.0 kcal/mol compared to ciprofloxacin − 7.2 kcal/mol, whereas analysis against human topoisomerase IIα showed binding energy value ranging from − 5.9 to − 5.3 kcal/mol compared to vosaroxin (− 6.2 kcal/mol). Conclusion: The results obtained suggest that N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol ( 1) and coumarin ( 5) are potential topoisomerase II α inhibitors and might be used as anticancer agents. The ADMET studies showed the highest drug-likeness properties for studied compounds other than bis(2-ethylheptyl) phthalate ( 3). DFT calculations suggested that studied compounds showed the lowest gap energy and were chemically reactive, and isolated compounds may serve as potential drug candidates that corroborate with the traditional uses of studied plants.

Introduction: In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid ( 1) and three coumarins ( 2– 4) isolated from roots of Clausena anisata. Methods: Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. SwissADME prediction and toxicological predictions were performed by ADMET. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels. Results and Discussion: The docking results revealed that compound 3 showed better docking scores against both DNA gyrase B and LasR binding domain compared with ciprofloxacin with potential as an inhibitor of bacterial DNA gyrase and quorum sensing LasR binding domain. The SwissADME prediction results showed that all the isolated compounds ( 1– 4) satisfy Lipinski’s rule of five with zero violations. Toxicological prediction results suggested that all compounds and ciprofloxacin are non-hepatotoxic, non-carcinogenic, non-irritant, immunogenic, and non-cytotoxic. The DFT analysis results revealed that compound 3 has large electronegativity (χeV), global softness (σ eV^{− 1}), global electrophilicity (ωeV), and mutagenicity value closer to ciprofloxacin (with LD₅₀ value of 480 mg/kg) suggesting better bioactivity and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups. Conclusion: Overall, compound 3 may serve as a lead molecule that could be developed into a potent E. coli DNA gyrase B inhibitor and efficient inhibitor for quorum sensing auto-inducer LasR binding domain of Pseudomonas aeruginosa.

Clausena anisata is one of the medicinal plants used traditionally for treatment of parasitic infections, irritation (boils, ringworm, and eczema), flatworm infestations, influenza, abdominal cramps, and constipation. Phytochemical screening test of dichloromethane/methanol (1 : 1) roots extract revealed the presence of flavonoids, phytosterols, coumarins, phenols, alkaloids, tannins, terpenoids, and free reducing sugars and the absence of saponins. Silica gel column chromatographic separation of the dichloromethane/methanol (1 : 1) extract afforded a carbazole alkaloid derivative of heptazoline (1) and three coumarins (2–4), including the known coumarins imperatorin (3) and chalepin (4). Structures of the compounds were elucidated by spectroscopic techniques (IR, ¹H NMR, ¹³C NMR, and DEPT-135). Antibacterial activity of the crude extracts and isolated compounds was screened using agar diffusion method against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus substilis. The results of antibacterial test revealed derivative of heptaphylline (1) and imperatorin (3) exhibited comparable antibacterial activity against S. aureus and B. substilis (14 and 13 mm zone of inhibition, respectively) to that of ciprofloxacin (15 mm zone of inhibition) at a concentration of 20 µg/mL. Chalepin (4) revealed more antibacterial activity against B. substilis (16 mm zone of inhibition) compared to ciprofloxacin (15 mm).

The dichloromethane/methanol (1 : 1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC₅₀ = 0.9–3 µg/mL) in vitro antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. Chromatographic separation of the extract of Pentas longiflora led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC₅₀ values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones (4–11, IC₅₀ = 5–31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three – nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10) – are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.

Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-O-methyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities.