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Background. Methicillin‐resistant Staphylococcus aureus (MRSA) is one of the major pathogens associated with life‐threatening infections, showing resistance to various antibiotics. This study aimed to assess the influence of monolaurin on biofilm‐forming MRSA. Methods. The agar dilution method determined the minimum inhibitory concentration (MIC) of monolaurin against MRSA isolates and explored its impact on the resistance profile of selected antibiotics. The assessment of combined therapy involving monolaurin and antibiotics was conducted using fractional inhibitory concentration (FIC). The tissue culture plate strategy appraised monolaurin's antibiofilm activity and its inhibitory concentration (IC50), with assessment via scanning electron microscopy. Reverse transcription polymerase chain reaction (RT‐PCR) discerned a monolaurin effect on the expression of the icaD gene. Results. Monolaurin exhibited MIC values ranging from 500 to 2000 μg/mL. FIC index showed a synergistic effect of monolaurin with β‐lactam antibiotics ranging from 0.0039 to 0.25 (p < 0.001). Among the 103 investigated MRSA isolates, 44 (44.7%) displayed moderate biofilm formation, while 59 (55.3%) were strong biofilm producers. Antibiofilm activity demonstrated concentration dependence, confirming monolaurin's capacity to inhibit biofilm formation and exhibited strong eradicating effects against preformed MRSA biofilms with IC50 values of 203.6 μg/mL and 379.3 μg/mL, respectively. Scanning electron microscope analysis revealed reduced cell attachments and diminished biofilm formation compared to the control. The expression levels of the icaD gene were remarkably reduced at monolaurin concentrations of 250 and 500 μg/mL. Conclusion. Monolaurin had significant inhibitory effects on MRSA pre‐existing biofilms as well as biofilm development. So, it can be employed in the treatment of severe infections, particularly those associated with biofilm formation including catheter‐associated infections. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied. Objectives: In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT). Methods: Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells. Results: No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed. Conclusion: This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance. [ABSTRACT FROM AUTHOR]

Fractionation of the stem bark of Enantia chlorantha Oliv yields three alkaloids, palmatine (1), jatrorrhizine (2), columbamine (3), and β-Sitosterol (4). In this investigation, density functional theory (DFT) calculations were carried out to evaluate the electronic structure and properties of 1–4 by DFT-B3LYP/6-31G level of theory using Gaussian 09 software. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), HOMO-LUMO energy difference (band gap), hardness (η), softness (S), dipole moment (μ), electronegativity (χ), hydrophobicity (logP), topological surface area (TPSA), and energy gap (Eg) were calculated. The in vitro cytotoxicity of the compounds was investigated against MCF-7 and HCT116 cancer cell lines using Wi-38 cells as a control. The compounds inhibited the proliferation of the MCF-7 and HCT116 cell lines and induced apoptosis via upregulation of caspase-3, Bax, PARP cleavage, and downregulation of Bcl-2. DFT analyses revealed that compounds 1 and 3 have smaller energy gaps, 0.072 and 0.071eV, respectively, with the highest dipole moments; hence, these compounds are more chemically reactive and exhibit better modulation of caspase-3 enzyme and inhibitory activities of the MCF-3 and HCT116 cell lines. The antimicrobial and antiparasitic evaluation of 1–4 showed moderate efficacy against the bacterial strains and moderate antiparasitic activity against Cichlidogyrus tilapia. [ABSTRACT FROM AUTHOR]

Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin (SP) and clarithromycin (CL) showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin (AZ) and CL exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin (ER) and roxithromycin (RO). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics. Molecular docking studies of 139 antibiotics against the topoisomerase II-DNA complex. SP, RO, AZ, CL, and ER were the most promising and commercially available candidates. Molecular dynamics simulations for 200 ns for the most promising five complexes. MM-GBSA calculations for the frontier five complexes. SP and CL showed promising anticancer potentials on the MCF-7 cell line, besides, AZ and CL exhibited good anticancer potentials against the HCT-116 cell line. Potent TOP-2 inhibitory potentials were recorded for ER and RO. [ABSTRACT FROM AUTHOR]

Three novel series of N-methylsulfonylindole derivatives 3a&b, 4a–e, and 5a–e were synthesised. Different biological activities of the synthesised compounds were studied. Antimicrobial activity showed that, compounds 4b, 4e and 5d had selective antibacterial activity against the Gram-negative bacteria, Salmonella enterica and/or E. coli. The anti-oxidant activity of the synthesised compounds was evaluated by DPPH radical scavenging activity. In vitro anti-inflammatory activity was estimated. Compounds 4d, 4e, 5b, and 5d showed the highest anti-inflammatory activity. The COX-1, COX-2 and 5-LOX inhibitory activities were measured using enzyme immune assay (EIA) kits. Due to the dual COX-2/5-LOX inhibitory activity of compound 5d, its cardiovascular profile was determined by measuring cardiac biomarkers (LDH, CK-MB, and Tn-I). Besides, the histopathological study of the heart muscle and stomach were examined for the most active COX-2 inhibitors 4e and 5d. Finally, a molecular modelling study and pharmacokinetic properties were obtained using different computational methods. [ABSTRACT FROM AUTHOR]

New spiro-piperidine derivatives were synthesised via the eco-friendly ionic liquids in a one-pot fashion. The in vitro antileishmanial activity against Leishmania major promastigote and amastigote forms highlighted promising antileishmanial activity for most of the derivatives, with superior activity compared to miltefosine. The most active compounds 8a and 9a exhibited sub-micromolar range of activity, with IC50 values of 0.89 µM and 0.50 µM, respectively, compared to 8.08 µM of miltefosine. Furthermore, the antileishmanial activity reversal of these compounds via folic and folinic acids displayed comparable results to the positive control trimethoprim. This emphasises that their antileishmanial activity is through the antifolate mechanism via targeting DHFR and PTR1. The most active compounds showed superior selectivity and safety profile compared to miltefosine against VERO cells. Moreover, the docking experiments of 8a and 9a against Lm-PTR1 rationalised the observed in vitro activities. Molecular dynamics simulations confirmed a stable and high potential binding to Lm-PTR1. [ABSTRACT FROM AUTHOR]

Herein, synthesis of new designated azines-based naphthalene scaffold (3a–10) was assisted by CuCl2.2H2O for the first time. Their biological screening manifested that azines 3a, 4, 7, 9, and 10 exhibit effectual mushroom tyrosinase inhibition with IC50 values within the ambit of 3.75–12.36 µM. Mostly, azines 4 and 9 demonstrated about four-fold enhancement in the activity (IC50 = 3.91 ± 0.16, 3.75 ± 0.15 µM, respectively) comparable to the kojic acid (IC50 = 16.86 ± 0.84 µM). Molecular docking of azines 4 and 9 against mushroom tyrosinase (2Y9X) proved the significant rule of isatin moiety (4) in hydrogen bonding, the importance of 4-dimethylamino styryl unit (9) in hydrophobic interactions, and the overall findings confirmed the momentousness of azine group (N–N) and naphthalene scaffold in the interactions with the histidine key residues of the tyrosinase binding pocket. Evaluation of antiproliferative activity indicated that, azine 4 was the most potent one against both MCF-7 and HCT116 with IC50 values of 4.35 ± 0.18 and 2.41 ± 0.12 µM, respectively. Whereas 9 was the most robust azine toward HepG2 with an IC50 value of 2.19 ± 0.12 µM. Exhaustively, azines 4 and 9 could be promising biomedical lead candidates. [ABSTRACT FROM AUTHOR]

Recently, the financial performance of the steel industry has faced several challenges due to a lack of focus on corporate social responsibilities (CSR), green finance, and information communication technology (ICT). Hence, this study investigates the impact of CSR, green finance, and ICT on the financial performance of the steel industry in China. The present research also investigates the moderating role of organizational support among CSR and firm performance and ICT and firm performance. We applied structural equation modeling to analyze the primary data of 290 employees collected from the employees of the steel industry in China. The findings indicated that CSR, green finance, and ICT have a positive and significant impact on the financial performance of this industry. The results also showed that organizational support significantly and positively moderates the interaction between CSR, ICT, and financial performance. These findings suggest that Chinese steel industries should adopt CSR practices and implement an ICT adoption strategy for better financial performance. [ABSTRACT FROM AUTHOR]