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Computer aided toxicity and pharmacokinetic prediction studies attracted the attention of pharmaceutical industries as an alternative means to predict potential drug candidates. In the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, toxicity profiles of sixteen antidiabetic flavonoids that have ideal bidentate chelating sites for metal ion coordination were examined using SwissADME, Pro Tox II, vNN and ADMETlab web tools. Density functional theory (DFT) calculations were also employed to calculate quantum chemical descriptors of the compounds. Molecular docking studies against human alpha amylase were also conducted. The results were compared with the control drugs, metformin and acarbose. The drug-likeness prediction results showed that all flavonoids, except myricetin, were found to obey Lipinski’s rule of five for their drug like molecular nature. Pharmacokinetically, chrysin, wogonin, genistein, baicalein, and apigenin showed best absorption profile with human intestinal absorption (HIA) value of ≥ 30%, compared to the other flavonoids. Baicalein, butein, ellagic acid, eriodyctiol, Fisetin and quercetin were predicted to show carcinogenicity. The flavonoid derivatives considered in this study are predicted to be suitable molecules for CYP3A probes, except eriodyctiol which interacts with P-glycoprotein (p-gp). The toxicological endpoints prediction analysis showed that the median lethal dose (LD 50 ) values range from 159–3919 mg/Kg, of which baicalein and quercetin are found to be mutagenic whereas butein is found to be the only immunotoxin. Molecular docking studies showed that the significant interaction (-7.5 to -8.3 kcal/mol) of the studied molecules in the binding pocket of the α-amylase protein relative to the control metformin with the crucial amino acids Asp 197, Glu 233, Asp 197, Glu 233, Trp 59, Tyr 62, His 101, Leu 162, Arg 195, His 299 and Leu 165. Chrysin was predicted to be a ligand with high absorption and lipophilicity with 84.6% absorption compared to metformin (78.3%). Moreover, quantum chemical, ADMET, drug-likeness and molecular docking profiles predicted that chrysin is a good bidentate ligand.

BackgroundThiazole-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.ResultsAmong the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values 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 compounds 9 and 11 (− 6.9, and − 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed 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.ConclusionsThe synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were 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.

Cancer is characterized by abnormal cell differentiation in or on the part of the body. The most commonly used chemotherapeutic drugs are developed to target rapidly dividing cells, such as cancer cells, but they also damage healthy epithelial cells. This has serious consequences for normal cells and become responsible for the development of various disorders. Several strategies for delivering the cytotoxic drugs to cancerous sites that limit systemic toxicity and other adverse effects have recently been evolved. Among them, biomolecule-conjugated metal complexes-based cancer targeting strategies have shown tremendous advantages in cancer therapy. This review focuses on several chemoselective biomolecules-bound metal complexes as prospective cancer therapy-targeted agents. In this review, we presented the details of the various extra- and intracellular targeting mechanisms in cancer therapy. We also addressed the current clinical issues and recent therapeutic strategies in targeted cancer therapy that may pave a way for the future direction of metal complexes-based targeted cancer therapy.

Thiazole-pyrazoline Schiff base hybrids have a broad range of pharmacological potential with an ability to control the activity of numerous metabolic enzymes. In this work, a greener and more efficient approach has been developed to synthesize a novel series of thiazole-pyrazoline Schiff base hybrids using ZnO nanoparticle-assisted protocol in good to excellent yields (78.3–96.9%) and examined their antibacterial activity against Gram-positive and Gram-negative bacteria, as well as their antioxidant activity. Compound 24 (IZD = 18.67 ± 0.58) displayed better activity against P. aeruginosa compared with amoxicillin (IZD = 14.33 ± 2.52) at 250 μg/mL, whereas compounds 22 and 24 (IZD = 13.33 ± 0.58 mm and 17.00 ± 1.00 mm, respectively) showed better activity against E. coli compared with amoxicillin (IZD = 14.67 ± 0.58 mm) at 500 μg/mL. The remaining compounds showed moderate to weak activity against the tested bacterial strains. Compound 21 displayed significant inhibition of DPPH (IC50 = 4.63 μg/mL) compared with ascorbic acid (IC50 = 3.21 μg/mL). Compound 21 displayed 80.01 ± 0.07% inhibition of peroxide formation, suggesting its potential in preventing the formation of lipid peroxides. The results of the ADMET study showed that all synthesized compounds obeyed Lipinski's rule of five. In silico pharmacokinetic study demonstrated that compound 24 had superior intestinal absorption compared with amoxicillin. In silico molecular docking analysis revealed a binding affinity of −9.9 Kcal/mol for compound 24 against PqsA compared with amoxicillin (−7.3 Kcal/mol), whereas compounds 22 and 24 displayed higher binding affinity (−8.5 and −7.9 Kcal/mol, respectively) with DNA gyrase B compared with amoxicillin (-7.1 Kcal/mol), in good agreement with in vitro antibacterial activity against P. aeruginosa and E. coli. In silico toxicity study showed that all synthesized compounds had LD50 (mg/kg) values ranging from 800 to 1,000 putting them in ProTox-II class 4. The in vitro antibacterial activity and molecular docking analysis showed that compound 24 is a promising antibacterial therapeutic agent against P. aeruginosa and E. coli and compound 22 is a promising antibacterial agent against E. coli, whereas compound 21 is found to be a potential natural antioxidant agent. Moreover, the green synthesis approach using ZnO nanoparticle as catalyst was found to be a very efficient method to synthesize biologically active thiazole-pyrazoline Schiff base hybrids compared with the conventional method.

Domestic sheep (Ovis aries) have adapted to diverse ecological regions and exhibit various phenotypic traits through long-term natural and artificial selection. Indigenous sheep populations, in particular, have developed valuable traits such as disease resistance, heat tolerance, and resilience to harsh environments. Understanding the genetic mechanisms underlying these adaptive traits is crucial for enhancing, sustainably utilizing, and conserving sheep genetic resources. In this study, we aimed to assess genomic selection among five Ethiopian indigenous sheep populations sampled from various ecological regions. Whole blood samples were randomly collected from 48 sheep representing two populations (Semien and Selale) from different ecological regions and genotyped using the Ovine 50K SNP BeadChip. Genotype data from three Ethiopian sheep populations was additionally included in the analyses. Fixation index (FST) and cross-population extended haplotype homozygosity (XPEHH) methods were used to detect signatures of positive selection. Functional analysis revealed genes related to plateau adaptation, immune response, and tail fat formation. Our study identified potential genes associated with alpine and sub-alpine adaptation, including GABRG3, SYT1, TGFBR3, ITPR2, KCNMB2, and ATP1A3. Candidate genes linked with wet highland adaptation, including GNB1, HDAC9, IGFBP6, JAKMIP1, PAK2, and EXOC4, were also detected as under selection. The BMP2 gene, known for its fundamental role in sheep adipose tissue, emerged as a positional candidate gene for tail fat formation. This study offers novel insight into genomic adaptation to alpine, sub-alpine, and wet highland ecological regions in sheep and provides a valuable resource for further investigation. Moreover, it contributes worthwhile information for sustainable conservation and utilization, and lays the groundwork for future research into the genetic mechanisms behind sheep adaptability to diverse ecological regions.

Myricasalicifolia A Rich (Myricaceae) is a tree growing in Central and East Africa. Traditionally, the plant is used to treat malaria, respiratory disorders, inflammations, and infections. A new compound, 3β-O-trans-caffeoylisomyricadiol (7), was isolated from MeOH : CHCl3 (2 : 1) extract of the stem bark of Myrica salicifolia along with seven known compounds, namely, myricanone (1), myricanol (2), myricanol-11-O-β-D-xylopyranoside (3), taraxerone (4), taraxerol (5), myricadiol (6), and methyl-β-D-glucopyranoside (8). This is the first report of the isolation of taraxerene-type triterpenes from this plant. The structures were determined by a comprehensive analysis of 1D/2D NMR spectroscopy, HR-MS, and by comparison with literature data. The compounds showed a wide range of DPPH scavenging activities from very weak (IC50 value = 282.61 μM) to very strong (IC50 = 13.48 μM). Antibacterial activities of the compounds were evaluated using the disk diffusion agar method, where some of the compounds showed modest antibacterial activities against S. pyogenes and S. aureus at 250 μg/mL. Compounds 2, 3, and 7 were assessed for their in silico molecular docking analysis. The lowest binding affinity for compound 7 was found to be −7.26 to −10.35 kcal/mol against PqsA protein of P. aeruginosa, pyruvate kinase (PK) enzyme of S. aureus, LuxS protein of S. pyogenes, and DNA gyrase B of E. coli, which showed better binding affinity compared to the standard drug ampicillin (−7.36 to −8.03 kcal/mol) and ciprofloxacin (−6.19 to −6.83 kcal/mol). In silico ADMET predictions revealed that compounds 3 and 8 met all the requirements for pharmacokinetic properties.

In the present study, a new series of nine Thiazolo[3,2-α] pyrimidine analogs were synthesized in good to excellent yields (87.9–96.9%) and improved reaction time using a ZnO nanoparticle-assisted protocol. All the synthesized compounds were characterized using a combination of physicochemical parameters, UV-visible, 1H-NMR, and 13C-NMR spectroscopic methods. Among the synthesized compounds, the in vitro antibacterial activity displayed by compound 16 was higher (14.67 ± 0.58 mm at 500 μg/mL) against P. aeruginosa compared to amoxicillin (12.33 ± 0.58 mm at 500 μg/mL), whereas compounds 14 and 18 showed comparable activity (12.00 ± 0.00 mm and 12.33 ± 0.58 mm at 500 μg/mL and 250 μg/mL, respectively) against the same strain. The activities displayed by compounds 14, 16, 18, and 20 were comparable (12.33 ± 1.15 mm, 12.65 ± 0.58 mm, 12.33 ± 0.58 mm, and 12.00 ± 1.00 mm, respectively, at 500 μg/mL) to amoxicillin (13.33 ± 1.15 mm at the same concentration) against E. coli. Compound 19 showed good activity (12.00 ± 1.72 mm at 500 μg/mL) against S. aureus compared to amoxicillin (16.33 ± 0.58 mm at the same concentration). Compound 19 displayed the highest percent inhibition of DPPH with an IC50 value of 9.48 g/mL using the DPPH free radical scavenging assay compared to ascorbic acid (3.21 g/mL) and promising inhibition of peroxide formation (76.28 ± 0.12%), demonstrating its potential in preventing the formation of lipid peroxides. Thus, according to our findings, both the biological activities and in silico computational results revealed that compounds 14, 16, and 18 are good antibacterial agents against P. aeruginosa and E. coli, whereas compound 19 was found to be a promising antibacterial agent against S. aureus and an antioxidant agent. The present study revealed that the synthesized compounds appear to be lead compounds for rational drug design.

Computer aided toxicity and pharmacokinetic prediction studies attracted the attention of pharmaceutical industries as an alternative means to predict potential drug candidates. In the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, toxicity profiles of sixteen antidiabetic flavonoids that have ideal bidentate chelating sites for metal ion coordination were examined using SwissADME, Pro Tox II, vNN and ADMETlab web tools. Density functional theory (DFT) calculations were also employed to calculate quantum chemical descriptors of the compounds. Molecular docking studies against human alpha amylase were also conducted. The results were compared with the control drugs, metformin and acarbose. The drug-likeness prediction results showed that all flavonoids, except myricetin, were found to obey Lipinski’s rule of five for their drug like molecular nature. Pharmacokinetically, chrysin, wogonin, genistein, baicalein, and apigenin showed best absorption profile with human intestinal absorption (HIA) value of ≥ 30%, compared to the other flavonoids. Baicalein, butein, ellagic acid, eriodyctiol, Fisetin and quercetin were predicted to show carcinogenicity. The flavonoid derivatives considered in this study are predicted to be suitable molecules for CYP3A probes, except eriodyctiol which interacts with P-glycoprotein (p-gp). The toxicological endpoints prediction analysis showed that the median lethal dose (LD50) values range from 159–3919 mg/Kg, of which baicalein and quercetin are found to be mutagenic whereas butein is found to be the only immunotoxin. Molecular docking studies showed that the significant interaction (-7.5 to -8.3 kcal/mol) of the studied molecules in the binding pocket of the α-amylase protein relative to the control metformin with the crucial amino acids Asp 197, Glu 233, Asp 197, Glu 233, Trp 59, Tyr 62, His 101, Leu 162, Arg 195, His 299 and Leu 165. Chrysin was predicted to be a ligand with high absorption and lipophilicity with 84.6% absorption compared to metformin (78.3%). Moreover, quantum chemical, ADMET, drug-likeness and molecular docking profiles predicted that chrysin is a good bidentate ligand.

is a medicinal plant traditionally used to treat various ailments. Limited studies on inspired us to investigate the chemical nature and therapeutic potential of the plant. Silica gel column chromatographic separation was used for isolation. 1D and 2D NMR spectroscopic analysis and literature data were used for structural elucidation. Agar well diffusion assay was used for evaluation of antibacterial activity against , and . DPPH assay was used to evaluate radical scavenging activities. Molecular docking was done by AutoDock Vina 4.2 open-source program. DFT calculations were performed using the Gaussian 16 program package. Dichloromethane/methanol (1:1) roots extract afforded a new hydroxyl-spongiane diterpenoid lactone derivative, 3-hydroxyisoagatholactone ( ), along with β-sitosterol ( ) and ε-viniferin ( ) whereas methanol extract afforded resveratrol ( ), gnetin H ( ), tricuspidatol A ( ), ε-viniferin-diol ( ) and parthenostilbenin B ( ). At 50 μg/mL, compound recorded the highest inhibition against (8.55 ± 0.45 mm) and (9.30 ±1.39 mm). Against , compound consistently outperformed chloramphenicol (11.76 ± 0.77 mm, at 30 g/mL). Maximum binding affinity were observed by compound 3 against DNA gyrase B (-7.6 kcal/mol) where as compound 5 displayed maximum binding against PqsA (-8.8 kcal/mol) and S. aureus PK (-5.8 kcal/mol). Compounds and satisfy Lipinski's rule of five. resveratrol ( ) demonstrated strong DPPH scavenging activity at 12.5 g/mL, with IC values of 0.052 µg/mL, compared to ascorbic acid (IC value of 0.0012 µg/mL). In this work, eight compounds were identified from the roots extracts of including a new hydroxyl-spongiane diterpenoid lactone, 3-hydroxyisoagatholactone ( ). Compounds and exhibited good antibacterial activity and binding affinities. The docking result is in agreement with the antibacterial study. Overall, the study result suggests that the isolated compounds have the potential to be used as therapeutic agents, which supports the traditional uses of roots.

Taye Demissie relates unununium’s unusually smooth route to roentgenium, and how predicting its properties relies on relativistic calculations.