Hydroxypropyl chitosan/ε-poly-l-lysine based injectable and self-healing hydrogels with antimicrobial and hemostatic activity for wound repair.

The biggest obstacle to treating wound healing continues to be the production of simple, inexpensive wound dressings that satisfy the demands associated with full process of repair at the same time. Herein, a series of injectable composite hydrogels were successfully prepared by a one-pot method by utilizing the Schiff base reaction as well as hydrogen bonding forces between hydroxypropyl chitosan (HCS), ε-poly-l-lysine (EPL), and 2,3,4-trihydroxybenzaldehyde (TBA), and multiple cross-links formed by the reversible coordination between iron (III) and pyrogallol moieties. Notably, hydrogel exhibits excellent physicochemical properties, including injectability, self-healing, water retention, and adhesion, which enable to fill irregular wounds for a long period, providing a suitable moist environment for wound healing. Interestingly, the excellent hemostatic properties of the hydrogel can quickly stop bleeding and avoid the serious sequelae of massive blood loss in acute trauma. Moreover, the powerful antimicrobial and antioxidant properties also protect against bacterial infections and reduce inflammation at the wound site, thus promoting healing at all stages of the wound. The study of biohydrogel with multifunctional integration of wound treatment and smart medical treatment is clarified by this line of research.

Oxidovanadium(V) Schiff Base Complexes Derived from Chiral 3-amino-1,2-propanediol Enantiomers: Synthesis, Spectroscopic Studies, Catalytic and Biological Activity.

Oxidovanadium(V) complexes, [(+)VOL1-5] and [(-)VOL1-5], with chiral tetradentate Schiff bases, which are products of monocondensation of S(‒)-3-amino-1,2-propanediol or R(+)-3-amino-1,2-propanediol with salicylaldehyde derivatives, have been synthesized. Different spectroscopic methods, viz. 1H and 51V NMR, IR, UV-Vis, and circular dichroism, as well as elemental analysis, have been used for their detailed characterization. Furthermore, the epoxidation of styrene, cyclohexene, and two monoterpenes, S(‒)-limonene and (‒)-α-pinene, using two oxidants, aqueous 30% H2O2 or tert-butyl hydroperoxide (TBHP) in decane, has been studied with catalytic amounts of all complexes. Finally, biological cytotoxicity studies have also been performed with these oxidovanadium(V) compounds for comparison with cis-dioxidomolybdenum(VI) Schiff base complexes with the same chiral ligands, as well as to determine the cytoprotection against the oxidative damage caused by 30% H2O2 in the HT-22 hippocampal neuronal cells in the range of their 10-100 µM concentration.

Synthesis, antimicrobial activity, antioxidant activity and molecular docking of novel chitosan derivatives containing glycine Schiff bases as potential succinate dehydrogenase inhibitors.

Succinate dehydrogenase (SDH) is an important inner mitochondrial membrane-bound enzyme involved in redox reactions during the tricarboxylic acid cycle. Therefore, a series of novel chitosan derivatives were designed and synthesized as potential microbicides targeting SDH and precisely characterized by FTIR, 1H NMR and SEM. Their antifungal and antibacterial activities were evaluated against Botrytis cinerea, Fusarium graminearum, Staphylococcus aureus and Escherichia coli. The bioassays revealed that these chitosan derivatives exerted significant antifungal effects, with four of the compounds achieving 100 % inhibition of Fusarium graminearum merely at a concentration of 0.5 mg/mL. Additionally, CSGDCH showed 79.34 % inhibition of Botrytis cinerea at a concentration of 0.1 mg/mL. In vitro antibacterial tests revealed that CSGDCH and CSGDBH have excellent Staphylococcus aureus and Escherichia coli inhibition with MICs of 0.0156 mg/mL and 0.03125 mg/mL, respectively. Molecular docking studies have been carried out to explore the binding energy and binding mode of chitosan and chitosan derivatives with SDH. The analyses indicated that chitosan derivatives targeted the active site of the SDH protein more precisely, disrupting its normal function and ultimately repressing the growth of microbial cells. Furthermore, the chitosan derivatives were also evaluated biologically for antioxidation, and all of these compounds had a greater degree of reducing power, superoxide radical, hydroxyl radical and DPPH-radical scavenging activity than chitosan. This research has the potential for the development of agricultural antimicrobial agents.

Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer.

Overcoming multidrug resistance (MDR) is one of the major challenges in cancer therapy. In this respect, Schiff base-related compounds (bearing a R1R2CNR3 bond) gained high interest during the past decades. Schiff bases are considered privileged ligands for various reasons, including the easiness of their preparation and the possibility to form complexes with almost all transition metal ions. Schiff bases and their metal complexes exhibit many types of biological activities and are used for the treatment and diagnosis of various diseases. Until now, 13 Schiff bases have been investigated in clinical trials for cancer treatment and hypoxia imaging. This review represents the first collection of Schiff bases and their complexes which demonstrated MDR-reversal activity. The areas of drug resistance covered in this article involve: 1) Modulation of ABC transporter function, 2) Targeting lysosomal ABCB1 overexpression, 3) Circumvention of ABC transporter-mediated drug efflux by alternative routes of drug uptake, 4) Selective activity against MDR cancer models (collateral sensitivity), 5) Targeting GSH-detoxifying systems, 6) Overcoming apoptosis resistance by inducing necrosis and paraptosis, 7) Reactivation of mutated p53, 8) Restoration of sensitivity to DNA-damaging anticancer therapy, and 9) Overcoming drug resistance through modulation of the immune system. Through this approach, we would like to draw attention to Schiff bases and their metal complexes representing highly interesting anticancer drug candidates with the ability to overcome MDR.

Zinc(II) Iminopyridine Complexes as Antibacterial Agents: A Structure-to-Activity Study.

Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies.

Synthesis of new quaternized chitosan Schiff bases and their N-alkyl derivatives as antimicrobial and anti-biofilm retardants in membrane technology.

New quaternized salicylidene chitosan Schiff bases (QSCSBs) and their N-octyl derivatives (OQCs) have been synthesized and characterized, aiming to develop innovative antimicrobial and anti-biofilm agents. This research holds immense potential, as these compounds could be utilized as anti-biofouling additives in membrane technology in the future. The synthesis involved the modification of low molecular-weight-chitosan (LMC) through simultaneous Schiff base formation and quaternization processes to create QSCSBs. Subsequently, QSCSBs were catalytically reduced to form quaternized N-benzyl chitosan (QBCs) intermediates, which then underwent nucleophilic substitution reactions affording N-octyl quaternized chitosans (OQCs). Characterization techniques such as elemental, spectral, and microscopic analyses were used to confirm the successful synthesis of these materials. As membrane technology relies on surface charge, QSCSBs and OQCs with large zeta potentials could be used as positively charged additives. Moreover, SEM image revealed the regular distribution of pores and voids across the additives' surfaces raises intriguing questions about their implications for membrane performance. Meanwhile, the superior antibacterial and antibiofilm potential of these materials, particularly QSCSB2 and OQC2, indicate that the utilization of these compounds as anti-biofouling additives in membrane technology could significantly improve the performance and longevity of membranes used in various applications such as water treatment and desalination.

New penta-Coordinated Cadmium(II) Complexes: Synthesis, Characterization, Thermal, Antimicrobial, Antioxidant and Cytotoxicity Properties.

In this paper, a new tridentate Schiff base ligand (L) with nitrogen donor atoms and its cadmium(II) complexes with the general formula of CdLX2 (X=Cl-, Br-, I-, SCN-, N3 -, NO3 -) have been synthesized and characterized by physical and spectral (FT/IR, UV-Vis, Mass, and 1H, 13C NMR spectroscopies) methods. Also nano-structured cadmium chloride and bromide complexes were synthesized by sonochemical method and then used to prepare nanostructured cadmium oxide confirmed by XRD and SEM techniques. Thermal behavior of the compounds was studied in the temperature range of 25 to 900 °C under N2 atmosphere at a heating rate of 20 °C/ min. Moreover, thermo-kinetic activation parameters of thermal decomposition steps were calculated according to the Coats-Redfern relationship. Antimicrobial activities of the synthesized compounds against two gram-positive and two gram-negative bacteria such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and two fungi of Candida albicans and Aspergillus niger were investigated by well diffusion method. SEM technique was used to monitor the morphological changes of the bacteria treated with the compounds. The 2,2-Diphenyl-1-picrylhydrazyl(DPPH) and the ferric reducing antioxidant power (FRAP) methods were used to evaluate the antioxidant ability of the ligand and its cadmium(II) complexes. In final, the cytotoxicity properties of the ligand and some cadmium(II) complexes against PC3 cancer cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) bioassay and nitric oxide (NO) level measurement. The morphological changes of prostate cancer (PC3) cells due to treatment with the ligand and its complexes confirmed their anticancer effectiveness.

1,2,3-triazole and chiral Schiff base hybrids as potential anticancer agents: DFT, molecular docking and ADME studies.

A series of novel 1,2,3-triazole and chiral Schiff base hybrids 2-6 were synthesized by Schiff base condensation reaction from pre-prepared parent component of the hybrids (1,2,3-triazole 1) and series of primary chiral amines and their chemical structure were confirmed using NMR and FTIR spectroscopies, and CHN elemental analysis. Compounds 1-6 were evaluated for their anticancer activity against two cancer PC3 (prostate) and A375 (skin) and MRC-5 (healthy) cell lines by Almar Blue assay method. The compounds exhibited significant cytotoxicity against the tested cancer cell lines. Among the tested compounds 3 and 6 showed very good activity for the inhibition of the cancer cell lines and low toxicity for the healthy cell lines. All the compounds exhibited high binding affinity for Androgen receptor modulators (PDB ID: 5t8e) and Human MIA (PDB ID: 1i1j) inhibitors compared to the reference anticancer drug (cisplatin). Structure activity relationships (SARs) of the tested compounds is in good agreement with DFT and molecular docking studies. The compounds exhibited desirable physicochemical properties for drug likeness.

Bioactive chitosan-citral Schiff base zinc complex: A pH-responsive platform for potential therapeutic applications.

The application of CO2 supercritical fluid (SCF) technology has developed rapidly because of its non-toxic, environmentally friendly, mild reaction conditions and safety. The SCF technology can effectively speed up the reaction process of nano-material synthesis, and maintains a high degree of controllability and repeatability. This study mainly included carboxymethyl chitosan sodium salt (CCS), citral (CT), p-coumaric acid (CA), and ZnSO4 as raw materials to prepare CCS-CT-CA-Zn complex as a pH-responsive agent and was investigated using supercritical fluid technique. The coordination structure of Bridge-CCS-CT-CH3COO-CA-Zn-Schiff base/OH and the morphology of the complex agents were verified. The prepared CCS-CT-CA-Zn complex showed good dispersion and uniformity (mean size: 852 ± 202 nm, PdI: 0.301, and mean zeta potential: -31 ± 6 mV). Also, it has a good pH responsive release in an acid environment. Besides, both of CCS-CT-CA-Zn complex (DS-B) and its decomposed mixture in acid (DS-A) demonstrated significant antioxidant and anti-vibrio activity. Moreover, both DS-B complex and DS-A mixture inhibited biofilm formation, swimming, and swarming motilities of V. parahaemolyticus in a dose-dependent manner. This work will provide a scientific basis for the further design and development of natural products derived antibacterial-antioxidant complex agents, food additives and feed additives.

19 Schiff bases as antimycobacterial agents: synthesis, molecular docking and a plausible mechanism of action.

Aim: To discover novel anti-Mycobacterium tuberculosis (Mtb) drugs, 19 compounds were synthesized; their anti-Mtb effects were evaluated and mechanisms of action were preliminarily explored. Materials & methods: The compounds were synthesized and their anti-Mtb activity was elucidated using resazurin microtiter assays. The plausible target of the potential compound was investigated by microimaging techniques, gas chromatography-mass spectrometry analysis and molecular docking. Results: 19 compounds inhibited Mtb growth with minimum inhibitory concentrations ranging from 1 to 32 µg/ml. Compounds 1-17 showed inhibition of Mtb KatG enzyme. Compound 19, the most potent, might be an inhibitor of Pks13 polyketide synthase. Conclusion: This study suggests that 2-((6-fluoropyridin-3-yl)methylene) hydrazine-1-carbothioamide (19) is a potential anti-Mtb lead compound with a novel mechanism of action.

Globally, more than 1.6 million people die of tuberculosis (TB) and about 11 million new cases occur each year. The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has made it difficult to effectively treat TB. Therefore, 19 drugs were synthesized and assayed in the laboratory to verify whether they could inhibit the growth of Mtb. All compounds exhibit anti-Mtb effects at relatively low concentrations. Among them, compound 19 had a strong anti-Mtb effect, and its bactericidal effect on Mtb even exceeded that of isoniazid. In addition, it was preliminarily determined that compound 19 is a novel inhibitor of a key enzyme in the biosynthesis of Mtb cell walls. These findings demonstrate a potential new treatment option for TB but more research is needed to confirm the safety of these drugs.

A novel isatin Schiff based cerium complex: synthesis, characterization, antimicrobial activity and molecular docking studies.

In this work, a novel isatin-Schiff base L2 had been synthesized through a simple reaction between isatin and 2-amino-5-methylthio-1,3,4-thiadiazole. The produced Schiff base L2 was then subjected to a hydrothermal reaction with cerium chloride to produce the cerium (III)-Schiff base complex C2. Several spectroscopic methods, including mass spectra, FT-IR, elemental analysis, UV-vis, 13C-NMR, 1H-NMR, Thermogravimetric Analysis, HR-TEM, and FE-SEM/EDX, were used to completely characterize the produced L2 and C2. A computer simulation was performed using the MOE software program to find out the probable biological resistance of studied compounds against the proteins in some types of bacteria or fungi. To investigate the interaction between the ligand and its complex, we conducted molecular docking simulations using the molecular operating environment (MOE). The docking simulation findings revealed that the complex displayed greater efficacy and demonstrated a stronger affinity for Avr2 effector protein from the fungal plant pathogen Fusarium oxysporum (code 5OD4) than the original ligand. The antibacterial activity of the ligand and its Ce3+ complex were applied in vitro tests against different microorganism. The study showed that the complex was found to be more effective than the ligand.

Synthesis and Antifungal Properties of 1,2,4-Triazole Schiff Base Agents Based on a 3D-QSAR Model.

Based on our previous research, a 3D-QSAR model (q2=0.51, ONC=5, r2=0.982, F=271.887, SEE=0.052) was established to predict the inhibitory effects of triazole Schiff base compounds on Fusarium graminearum, and its predictive ability was also confirmed through the statistical parameters. According to the results of the model design, 30 compounds with superior bioactivity compared to the template molecule 4 were obtained. Seven of these compounds (DES2-6, DES9-10) with improved biological activity and readily available raw materials were successfully synthesized. Their structures were confirmed through HRMS, NMR, and single crystal X-ray diffraction analysis (DES-5). The bioactivity of the final products was investigated through an in vitro antifungal assay. There was little difference in the EC50 values between the experimental and predicted values of the model, demonstrating the reliability of the model. Especially, DES-3 (EC50=9.915 mg/L) and DES-5 (EC50=9.384 mg/L) exhibited better inhibitory effects on Fusarium graminearum compared to the standard drug (SD) triadimenol (EC50=10.820 mg/L). These compounds could serve as potential new fungicides for future research. The interaction between the final products and isocitrate lyase (ICL) was investigated through molecular docking. Compounds with R groups that have a higher electron-donating capacity were found to be biologically active.

Synthesis, in vitro bio-evaluation and in silico molecular docking studies of thiadiazole-based Schiff base derivatives.

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that target drug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and -CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.

Pyrimidine Schiff Bases: Synthesis, Structural Characterization and Recent Studies on Biological Activities.

Recently, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine has been synthesized, characterized, and evaluated for its antibacterial activity against Enterococcus faecalis in combination with antineoplastic activity against gastric adenocarcinoma. In this study, new 5-iminomethylpyrimidine compounds were synthesized which differ in the substituent(s) of the aromatic ring attached to the imine group. The structures of newly obtained pyrimidine Schiff bases were established by spectroscopy techniques (ESI-MS, FTIR and 1H NMR). To extend the current knowledge about the features responsible for the biological activity of the new 5-iminomethylpyrimidine derivatives, low-temperature single-crystal X-ray analyses were carried out. For all studied crystals, intramolecular N-H∙∙∙N hydrogen bonds and intermolecular C-H∙∙∙F interactions were observed and seemed to play an essential role in the formation of the structures. Simultaneously, their biological properties based on their cytotoxic features were compared with the activities of the Schiff base (III) published previously. Moreover, computational investigations, such as ADME prediction analysis and molecular docking, were also performed on the most active new Schiff base (compound 4b). These results were compared with the highest active compound III.

Ligand-based virtual screening and biological evaluation of inhibitors of Mycobacterium tuberculosis H37Rv.

Novel antimycobacterial compounds are needed to expand the existing toolbox of therapeutic agents, which sometimes fail to be effective. In our study we extracted, filtered, and aggregated the diverse data on antimycobacterial activity of chemical compounds from the ChEMBL database version 24.1. These training sets were used to create the classification and regression models with PASS and GUSAR software. The IOC chemical library consisting of approximately 200,000 chemical compounds was screened using these (Q)SAR models to select novel compounds potentially having antimycobacterial activity. The QikProp tool (Schrödinger) was used to predict ADME properties and find compounds with acceptable ADME profiles. As a result, 20 chemical compounds were selected for further biological evaluation, of which 13 were the Schiff bases of isoniazid. To diversify the set of selected compounds we applied substructure filtering and selected an additional 10 compounds, none of which were Schiff bases of isoniazid. Thirty compounds selected using virtual screening were biologically evaluated in a REMA assay against the M. tuberculosis strain H37Rv. Twelve compounds demonstrated MIC below 20 µM (ranging from 2.17 to 16.67 µM) and 18 compounds demonstrated substantially higher MIC values. The discovered antimycobacterial agents represent different chemical classes.

Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action.

In an effort to develop new potent anticancer agents, two Schiff base rhenium(I) tricarbonyl complexes, containing the ubiquitous aminoquinoline scaffold, were synthesized. Both aminoquinoline ligands and Re(I) complexes showed adequate stability over a 48-h incubation period. Furthermore, the cytotoxic activity of the precursor ligands and rhenium(I) complexes were evaluated against the hormone-dependent MCF-7 and hormone-independent triple negative MDA-MB-231 breast cancer cell lines. Inclusion of the [Re(CO)3Cl]+ entity significantly enhanced the cytotoxicity of the aminoquinoline Schiff base ligands against the tested cancer cell lines. Remarkably, the incorporation of the Schiff-base iminoquinolyl entity notably enhanced the cytotoxic activity of the Re(I) complexes, in comparison with the iminopyridyl entity. Notably, the quinolyl-substituted complex showed up to three-fold higher activity than cisplatin against breast cancer cell lines, underpinning the significance of the quinoline pharmacophore in rational drug design. In addition, the most active Re(I) complex showed better selectivity towards the breast cancer cells over non-tumorigenic FG-0 cells. Western blotting revealed that the complexes increased levels of γH2AX, a key DNA damage response protein. Moreover, apoptosis was confirmed in both cell lines due to the detection of cleaved PARP. The complexes show favourable binding affinities towards both calf thymus DNA (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions align with their cytotoxic effects. The in silico molecular simulations of the complexes were also performed with CT-DNA and BSA targets.

Formulation of novel bioactive gelatin inspired by cinnamaldehyde for combating multi-drug resistant bacteria: Characterization, molecular docking, pharmacokinetic analyses, and in vitro assessments.

This study set out to formulate antibacterial and antioxidant gelatin boosted by cinnamaldehyde for combating multi-drug resistant bacteria previously obtained from chronic wounds. Towards this end, gelatin amine groups were conjugated with carbonyl groups of cinnamaldehyde, producing cinnamyl-gelatin Schiff bases. The physicochemical attributes of cinnamyl-gelatin Schiff bases were probed concerning alterations in chemical structures and microstructures compared to native gelatin. Besides, cinnamyl-gelatin Schiff bases exhibited higher thermal stability than gelatin, with a diminishing in solubility due to increases in hydrophobicity features. Interestingly, cinnamyl-gelatin derivatives exerted antibacterial activities versus multi-drug resistant Gram-negative and Gram-positive bacteria, showing maximum growth inhibition at the highest concentration of cinnamaldehyde incorporated into gelatin. The scavenging activities of gelatin against DPPH and ABTS•+ were promoted in cinnamyl-gelatin derivatives from 11.93 ± 0.6 % to 49.9 ± 2.5 % and 12.54 ± 0.63 % to 49.9 ± 3.12 %, respectively. Remarkably, cinnamyl-gelatin derivatives induced the proliferation of fibroblast cells, implying their prospective applications in tissue engineering. Molecular docking and pharmacokinetic investigations disclosed the potential antibacterial mechanisms of cinnamyl-gelatin derivatives alongside their biopharmaceutical applications. Altogether, these findings suggest that cinnamyl-gelatin derivatives could be utilized to tailor antibacterial-free antibiotics and antioxidant wound dressings against virulent bacteria to promote chronic wound recovery.

A trinuclear Zn (II) schiff base dicyanamide complex attenuates bacterial biofilm formation by ROS generation and membrane damage and exhibits anticancer activity.

A trinuclear Zn (II) complex, [(ZnL{N(CN)2})2Zn], termed complex 1 has been synthesized by the reaction of an aqueous solution of sodium dicyanamide to the methanolic solution of Zn (CH3COO)2, 2H2O and corresponding Schiff base (H2L) which is derived from 1:2 condensation of 1, 4 butane diamine with 3-ethoxy salicylaldehyde. Complex 1 is characterized by elemental analysis, IR, UV and Single X-ray diffraction study. Drug resistance is a growing global public health concern that has prompted researchers to look into advanced alternative treatment modalities. In this context, complex 1 has shown promising antibacterial and antibiofilm efficacy against gram-positive Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus strains. Complex 1 attenuated Staphylococcal biofilm formation by reducing several virulence factors including the formation of extracellular polysaccharide matrix, slime, haemolysin, staphyloxanthin, auto-aggregation, cell surface hydrophobicity, and motility. Notably, complex 1 mechanistically potentiated Reactive Oxygen Species (ROS) generation within the bacterial cells, leading to the damage of bacterial cell membrane followed by DNA leakage and thereby impeding the growth of Staphylococcus aureus. Furthermore, complex 1 significantly exhibited anticancer activity by reducing the growth of prostate adenocarcinoma cells. It obstructed the migration of cancer cells by potentiating apoptosis and arresting the cell cycle at the G2/M phase. In summary, complex 1 could act as a potent candidate for the generation of novel antibacterial, antibiofilm as well as anticancer treatment regimens for the management of drug-resistant biofilm-mediated Staphylococcus aureus infection and lethal prostate malignancy.

Synthesis and biological evaluation against H. pylori of chitosan menthone Schiff base hybrid with different types of inorganic nanoparticles.

The production of novel natural medicines for the treatment of Helicobacter pylori (H. pylori) has lately attracted a lot of interest. Some bacterial infections have traditionally been alleviated by terpenes. The present work intended to examine the impact of several chitosan menthone Schiff base nanocomposites on the treatment of H. pylori infection as well as on its anti-inflammatory capacity. Chitosan (Cs) was condensed with menthone with different molar ratios of Cs:menthone (1:0.5, 1:1, and 1:2) to produce chitosan Schiff bases namely; Cs-SB1, Cs-SB2, and Cs-SB3, respectively. Cs-SB3 Schiff base nanocomposites were prepared individually by adding 2%Ag, 2%Se, (1%Ag + 1%Se), and 2%Fe2O3 nanoparticles to produce compounds denoted as Cs-SB-Ag, Cs-SB-Se, Cs-SB-Ag/ Se, and Cs-SB-Fe, respectively. The anti-H. pylori activity of Cs-SB-Se was detected at a minimal inhibitory concentration MIC of 1.9 µg/mL making it the most biologically active compound in our study. Cs-SB-Se nanocomposite was tested for its cyclooxygenases (COX-1 and COX-2) inhibitory potential which demonstrated inhibitory efficacy towards COX enzymes with inhibition value against COX-1 (IC50 = 49.86 ± 1.784 µg/mL) and COX-2 (IC50 = 12.64 ± 0.463 µg/mL) which were less than the well-known Celecoxib (22.65 ± 0.081 and 0.789 ± 0.029 µg/mL) and Indomethacin (0.035 ± 0.001 and 0.08 ± 0.003 µg/mL) inhibitors. The selectivity index SI = 3.94 for tested nanocomposites indicated higher selectivity for COX-1. The cytotoxicity of the Cs-SB-Se nanocomposite was evaluated in Vero cells (CCL-81) and it showed that at a concentration of 62.5 µg/mL, cell viability was 85.43 %.

Comparative study on Antibacterial efficacy of a series of chromone sulfonamide derivatives against drug-resistant and MDR-isolates.

Sulfonamide derivatives have numerous pharmaceutical applications having antiviral, antibacterial, antifungal, antimalarial, anticancer, and antidepressant activities. The structural flexibility of sulfonamide derivatives makes them an excellent candidate for the development of new multi-target agents, although long-time exposure to sulfonamide drugs results in many toxic impacts on human health. However, sulfonamides may be functionalized for developing less toxic and more competent drugs. In this work, sulfonamides including Sulfapyridine (a), Sulfathiazole (b), Sulfamethoxazole (c), and Sulfamerazine (d) are used to synthesize Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbalde-hyde (1a-1d). The synthesized compounds were spectroscopically characterized and tested against hospital isolates of three Gram-positive (Methicillin-resistant Staphylococcus aureus PH217, Ampicillin-resistant Coagulase-negative Staphylococcus aureus, multidrug-resistant (MDR) Enterococcus faecalis PH007R) and two Gram-negative bacteria (multidrug-resistant Escherichia coli, and Salmonella enterica serovar Typhi), compared to the quality control strains from ATCC (S. aureus 29213, E. faecalis 25922, E. coli 29212) and MTCC (S. Typhi 734). Two of the four Schiff bases 1a and 1b are found to be more active than their counterpart 1c and 1d; while 1a have showed significant activity by inhibiting MRSA PH217 and MDR isolates of E. coli at the minimum inhibitory concentration (MIC) of 150 µg/mL and 128 µg/mL with MBC of 1024 µg/mL, respectively. On the other hand, the MIC of 1b was 150 µg/mL against both S. aureus ATCC 29213 and Salmonella Typhi MTCC 734, compared to the control antibiotics Ampicillin and Gentamycin. Scanning electron microscopy demonstrated the altered surface structure of bacterial cells as a possible mechanism of action, supported by the in-silico molecular docking analysis.