Design and synthesis of novel tetrabromophthalimide derivatives as potential tubulin inhibitors endowed with apoptotic induction for cancer treatment.

Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.

Green Biocatalyst for Ultrasound-Assisted Thiazole Derivatives: Synthesis, Antibacterial Evaluation, and Docking Analysis.

The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1H NMR, 13C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds.

Poly (Vinyl Alcohol) Hydrogels Boosted with Cross-Linked Chitosan and Silver Nanoparticles for Efficient Adsorption of Congo Red and Crystal Violet Dyes.

In our previous work, three different weight ratios of chitosan/PVA (1:3, 1:1, and 3:1) were blended and then cross-linked with trimellitic anhydride isothiocyanate (TAI) at a concentration depending on their chitosan content, obtaining three hydrogels symbolized by H13, H11, and H31. Pure chitosan was cross-linked with TAI, producing a hydrogel symbolized by H10. Further, three H31-based silver nanoparticles composites (H31/AgNPs1%, H31/AgNPs3%, and H31/AgNPs5%) were also synthesized. They were investigated, for the first time in this study, as adsorbents for Congo Red (CR) and Crystal Violet (CV) dyes. The removal efficiency of CR dye increased with increasing H10 content in the hydrogels, and with increasing AgNP content in the composites, reaching 99.91% for H31/AgNPs5%. For CV dye, the removal efficiency increased with the increase in the PVA content. Furthermore, the removal efficiency of CV dye increased with an increasing AgNP content, reaching 94.7% for H31/AgNPs5%. The adsorption capacity increased with the increase in both the initial dye concentration and temperature, while with an increasing pH it increased in the case of CV dye and decreased in the case of CR dye. The adsorption of CV dye demonstrated that the Freundlich isotherm model is better suited for the experimental results. Moreover, the results were best fitted with pseudo-second-order kinetic model.

Evaluation of the in vitro anti-inflammatory and anti-Helicobacter pylori activities of chitosan-based biomaterials modified with copper oxide nanoparticles.

For chemical modification, p-aminobenzoic acid was incorporated into chitosan Schiff base (ACsSB) and chitosan (ACs). Two ACs-based CuO nanoparticles composites; ACs/CuONPs-1 % and ACs/CuONPs-5 %, were also synthesized. Their structures were emphasized utilizing several analytical techniques; elemental analysis, FTIR, 1H NMR, XRD, SEM, EDX and TEM. Compared with standard cyclooxygenase (COX) inhibitor, Celecoxib, the prepared biomaterials showed in vitro selective inhibitory effectiveness against COX-2 enzyme that could be sorted, according to their MIC values that produce 50 % inhibition of COX-2 enzyme activity, as follows: Celecoxib (0.28 µg/mL) > ACs/CuONPs-5 % (4.1 µg/mL) > ACs/CuONPs-1 % (14.8 µg/mL) > ACs (38.5 µg/mL) > ACsSB (58.9 µg/mL) > chitosan (>125 µg/mL). Further, ACs/CuONPs-5 % has more in vitro inhibition efficiency towards Helicobacter pylori (H. pylori) than the other prepared biomaterials. Interestingly, the MIC value of 100 % growth inhibition of H. pylori for ACs/CuONP-5 % is equal to that of drug Clarithromycin (1.95 µg/mL). Thus, ACs/CuONPs-5 % has a promising potential as anti-H. pylori and selective anti-inflammatory agent. ACs/CuONPs-5 % is safe on the human gastric normal cells (GES-1). Therefore, amalgamation of both p-aminobenzoic acid and CuONPs into chitosan extremely promoted its anti-inflammatory and anti-H. pylori activity. This is a promising approach to achieve methods successful to compete the conventional antibiotics.

Reinforcement of the antimicrobial activity and biofilm inhibition of novel chitosan-based hydrogels utilizing zinc oxide nanoparticles.

Two novel chemically cross-linked chitosan hydrogels were successfully prepared via insertion of oxalyl dihydrazide moieties between chitosan Schiff's base chains (OCsSB) and between chitosan chains (OCs). For more modification, two different concentrations of ZnO nanoparticles (ZnONPs) were loaded into OCs to obtain OCs/ZnONPs-1 % and OCs/ZnONPs-3 % composites. The prepared samples were recognized using elemental analyses, FTIR, XRD, SEM, EDS and TEM. Their inhibitory action against microbes and biofilms were classified as: OCs/ZnONPs-3 % > OCs/ZnONPs-1 % > OCs > OCsSB > chitosan. OCs has inhibition activity similar to Vancomycin of minimum inhibitory concentration (MIC) value of 3.9 µg/mL against P. aeruginosa. OCs exhibited minimum biofilm inhibitory concentration (MBIC) values (from 31.25 to 62.5 µg/mL) less than that of OCsSB (from 62.5 to 250 µg/mL) which lower than that of chitosan (from 500 to 1000 µg/mL) against S. epidermidis, P. aeruginosa and C. albicans. OCs/ZnNPs-3 % showed MIC value (that caused 100 % inhibition of Clostridioides difficile, C. difficile) of 0.48 µg/mL much lower than Vancomycin (1.95 µg/mL). Both OCs and OCs/ZnONPs-3 % composite were safe on normal human cells. Thus, inclusion of oxalyl dihydrazide and ZnONPs into chitosan greatly reinforced its antimicrobial activity. This is a good strategy to accomplish adequate systems for competing traditional antibiotics.

Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity.

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.

Preparation and Characterization of a New Bis-Uracil Chitosan-Based Hydrogel as Efficient Adsorbent for Removal of Anionic Congo Red Dye.

A new hydrogel, based on chitosan crosslinked with 2-chlorophenyl-bis(6-amino-1,3-dimethyluracil-5-yl) methane, (2Clph-BU-Cs), has been successfully created. Various instrumental techniques such as elemental analysis, FTIR, SEM, and XRD were used to prove its structure. Its removal efficiency for anionic Congo red (CR) dye under different conditions for industrial wastewater treatment was studied. For optimizing the conditions to maximize CR dye removal, the impacts of temperature, contact time, pH, and initial concentration of the dye on adsorption capacity were investigated. The removal of the dye was pH-dependent, with a much higher value achieved at pH 4 than at pH 7 and 9. The maximum adsorption capacity of the hydrogel was 93.46 mg g-1. The model of adsorption process was fitted to the pseudo-second-order kinetic model. The intraparticle diffusion demonstrated the multi-step nature of the adsorption process. The thermodynamic results showed that the adsorption process was endothermic because of the positive value of enthalpy (43.70 kJ mol-1). The process of adsorption at high temperatures was spontaneous, according to the values of ∆G0. An increase in randomness was seen in the value of ∆S°. Generally, the investigated hydrogel has the potential to be used as a promising effective reusable adsorbent for industrial wastewater remediation.

Design, Synthesis, and Characterization of Novel Bis-Uracil Chitosan Hydrogels Modified with Zinc Oxide Nanoparticles for Boosting Their Antimicrobial Activity.

A new series of hydrogels was successfully prepared by incorporating various substituted bisuracil (R-BU) linkages between chitosan Schiff's base chains (R-BU-CsSB) and between chitosan chains (R-BU-Cs). After protection of the amino groups of chitosan by benzaldehyde, yielding chitosan Schiff's base (CsSB), the reaction with epichlorohydrin was confined on the -OH on C6 to produce epoxy chitosan Schiff's base (ECsSB), which was reacted with R-BU to form R-BU-CsSB hydrogels, and finally, the bioactive amino groups of chitosan were restored to obtain R-BU-Cs hydrogels. Further, some R-BU-Cs-based ZnO nanoparticle (R-BU-Cs/ZnONPs) composites were also prepared. Appropriate techniques such as elemental analysis, FTIR, XRD, SEM, and EDX were used to verify their structures. Their inhibition potency against all the tested microbes were arranged as: ZnONPs bio-composites > R-BU-Cs hydrogels > R-BU-CsSB hydrogels > Cs. Their inhibition performance against Gram-positive bacteria was better than Gram-negative ones. Their minimum inhibitory concentration (MIC) values decreased as a function of the negative resonance effect of the substituents in the aryl ring of R-BU linkages in the hydrogels. Compared with Vancomycin, the ZnONPs bio-composites showed superior inhibitory effects against most of the tested Gram-negative bacteria, all inspected Gram-positive ones, and all investigated fungi.

Evaluation of Antimicrobial and Anti-Biofilm Formation Activities of Novel Poly(vinyl alcohol) Hydrogels Reinforced with Crosslinked Chitosan and Silver Nano-Particles.

Novel hydrogels were prepared by blending chitosan and poly(vinyl alcohol), PVA, then crosslinking the resulting blends using trimellitic anhydride isothiocyanate at a concentration based on chitosan content in the blends. The weight ratios of chitosan: PVA in the blends were 1:3, 1:1, and 3:1 to produce three hydrogels symbolized as H13, H11, and H31, respectively. For a comparison, H10 was also prepared by crosslinking pure chitosan with trimellitic anhydride isothiocyanate. For further modification, three H31/silver nanocomposites (AgNPs) were synthesized using three different concentrations of silver nitrate to obtain H31/AgNPs1%, H31/AgNPs3% and H31/AgNPs5%. The structures of the prepared samples were emphasized using various analytical techniques. PVA has no inhibition activity against the tested microbes and biofilms. The antimicrobial and anti-biofilm formation activities of the investigated samples was arranged as: H31/AgNPs5% ≥ H31/AgNPs3% > H31/AgNPs1% > H10 > H31 > H11 > H13 > chitosan. H31/AgNPs5% and H31/AgNPs3% were more potent than Vancomycin and Amphotericin B against most of the tested microbes. Interestingly, H31 and H31/AgNPs3% were safe on the normal human cells. Consequently, hydrogels resulting from crosslinked blends of chitosan and PVA loaded with AgNPs in the same structure have significantly reinforced the antimicrobial and inhibition activity against the biofilms of PVA.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form.

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Evaluation of the antimicrobial and anti-biofilm activity of novel salicylhydrazido chitosan derivatives impregnated with titanium dioxide nanoparticles.

Two novel chitosan derivatives were prepared by incorporating salicylhydrazide into chitosan Schiff base (SCsSB) and chitosan (SCs). Two nanocomposites, SCs/TiO2-1% and SCs/TiO2-3%, were also prepared. Their structures were confirmed using elemental analyses, FTIR, XRD, SEM, EDX and TEM. Their antimicrobial and anti-biofilm activities were arranged as: SCs/TiO2-3% > SCs/TiO2-1% > SCs > SCsSB > chitosan. SCs showed minimum inhibitory concentration (MIC) value of 1.95 µg/mL against A. niger which was comparable with that of Amphotericin B. SCs/TiO2-3% showed higher inhibition against S. epidermidis, S. aureus, S. pyogenes, P. aeruginosa and E. coli than Vancomycin. While, it showed comparable inhibition activity to that of Vancomycin against B. subtilis and P. mirabilis. SCs/TiO2-3% showed MIC values equal 0.48 and 0.98 µg/mL corresponded to 0.98 and 1.95 µg/mL of Amphotericin B against C. albicans, A. fumigatus and A. niger, respectively. SCs/TiO2-3% showed much lower minimum biofilm inhibitory concentration (MBIC) values, ranged between 1.95 and 7.81 µg/mL, than those of SCs, ranged from 62.5 to 125 µg/mL. SCs/TiO2-3% was safe on normal human cells. The modifiers and TiO2 nanoparticles incorporated into chitosan in one structure developed its performance. It is approach for attaining appropriate structures which are good competitors for antimicrobial agents.

Synthesis and Characterization of Novel Uracil-Modified Chitosan as a Promising Adsorbent for Efficient Removal of Congo Red Dye.

Novel Uracil-modified chitosan (UCs) adsorbent has successfully been synthesized through a four-step method during which the amino groups of chitosan have been protected, then epoxy nuclei have been incorporated, afterwards the latter have been opened using 6-amino-1,3-dimethyl uracil, and finally the amino groups have been regained via removing the protection. Its structure was checked using FTIR, XRD and SEM techniques. The adsorption capacity of UCs for anionic Congo Red (CR) dye was studied under various conditions. It decreased significantly with increasing the solution pH value and dye concentration, while increased with increasing temperature. The adsorption of UCs for CR dye at different temperatures, solution pH and dye concentrations fitted to the kinetic model of pseudo-second order and Elovich model. The intraparticle diffusion model showed that the adsorption process involves multi-step process. The isotherm of CR dye adsorption by UCs conforms to the Langmuir isotherm model indicating the monolayer nature of adsorption. The maximum monolayer coverage capacity, qmax, was 434.78 mg g-1. Studying the thermodynamic showed that the adsorption of CR dye onto UCs was endothermic as illustrated from the positive value of enthalpy (21.37 kJ mol-1). According to the values of ΔG°, the adsorption process was spontaneous at all selected temperatures. The value of ΔS° showed an increase in randomness for the adsorption of CR dye by UCs. The value of activation energy was 18.40 kJ mol-1.

Kinetics, Isotherm and Thermodynamic Studies for Efficient Adsorption of Congo Red Dye from Aqueous Solution onto Novel Cyanoguanidine-Modified Chitosan Adsorbent.

Novel Cyanoguanidine-modified chitosan (CCs) adsorbent was successfully prepared via a four-step procedure; first by protection of the amino groups of chitosan, second by insertion of epoxide rings, third by opening the latter with cyanoguanidine, and fourth by restoring the amino groups through elimination of the protection. Its structure and morphology were checked using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The adsorption capacity of CCs for Congo Red (CR) dye was studied under various conditions. It decreased significantly with the increase in the solution pH value and dye concentration, while it increased with increasing temperature. The adsorption fitted to the pseudo-second order kinetic model and Elovich model. The intraparticle diffusion model showed that the adsorption involved a multi-step process. The isotherm of CR dye adsorption by CCs conforms to the Langmuir isotherm model, indicating the monolayer nature of adsorption. The maximum monolayer coverage capacity, qmax, was 666.67 mg g-1. Studying the thermodynamic showed that the adsorption was endothermic as illustrated from the positive value of enthalpy (34.49 kJ mol-1). According to the values of ΔG°, the adsorption process was spontaneous at all selected temperatures. The value of ΔS° showed an increase in randomness for the adsorption process. The value of activation energy was 2.47 kJ mol-1. The desorption percentage reached to 58% after 5 cycles. This proved that CCs is an efficient and a promising adsorbent for the removal of CR dye from its aqueous solution.

Adsorption Behavior of Methylene Blue Dye by Novel CrossLinked O-CM-Chitosan Hydrogel in Aqueous Solution: Kinetics, Isotherm and Thermodynamics.

The chemical cross-linking of carboxymethyl chitosan (O-CM-chitosan), as a method for its modification, was performed using trimellitic anhydride isothiocyanate to obtain novel cross-linked O-CM-chitosan hydrogel. Its structure was proven using FTIR, XRD and SEM. Its adsorption capacity for the removal of Methylene Blue (MB) dye from aqueous solution was studied. The effects of different factors on the adsorption process, such as the pH, temperature and concentration of the dye, in addition to applications of the kinetic studies of the adsorption process, adsorption isotherm and thermodynamic parameters, were studied. It was found that the amount of adsorbed MB dye increases with increasing temperature. A significant increase was obtained in the adsorption capacities and removal percentage of MB dye with increasing pH values. An increase in the initial dye concentration increases the adsorption capacities, and decreases the removal percentage. It was found that the pseudo-second-order mechanism is predominant, and the overall rate of the dye adsorption process appears to be controlled by more than one step. The Langmuir model showed high applicability for the adsorption of MB dye onto O-CM-chitosan hydrogel. The value of the activation energy (Ea) is 27.15 kJ mol-1 and the thermodynamic parameters were evaluated. The regeneration and reuse of the investigated adsorbent was investigated.

Cross-Linked Chitosan/Multi-Walled Carbon Nanotubes Composite as Ecofriendly Biocatalyst for Synthesis of Some Novel Benzil Bis-Thiazoles.

Aminohydrazide cross-linked chitosan (CLCS) and its MWCNTs (CLCS/MWCNTs) were formulated and utilized as a potent ecofriendly basic heterogeneous biocatalyst under ultrasonic irradiation for synthesis of two novel series of benzil bis-aryldiazenylthiazoles and benzil bis-arylhydrazonothiazolones from the reaction of benzil bis-thiosemicarbazone with 2-oxo-N'-arylpropanehydrazonoyl chlorides and ethyl 2-chloro-2-(2-phenylhydrazono) acetates, respectively. The chemical structures of the newly synthesized derivatives were elucidated by spectral data and alternative methods, where available. Additionally, their yield % was estimated using a traditional catalyst as TEA and green recyclable catalysts as CLCS and CLCS/MWCNTs composite in a comparative study. We observed that, under the same reaction conditions, the yield % of the desired products increased by changing TEA to CLCS then to CLCS/MWCNT from 72-78% to 79-83% to 84-87%, respectively. The thermal stability of the investigated samples could be arranged as CLCS/MWCNTs composite > CLCS > chitosan, where the weight losses of chitosan, CLCS and CLCS/MWCNTs composite at 500 °C were 65.46%, 57.95% and 53.29%, respectively.

Synthesis, characterization, anti-inflammatory and anti-Helicobacter pylori activities of novel benzophenone tetracarboxylimide benzoyl thiourea cross-linked chitosan hydrogels.

Chitosan (Cs) was cross-linked with four various quantities of 4,4'-(5,5'­carbonylbis(1,3-dioxoisoindoline-5,2-diyl))dibenzoyl isothiocyanate. Elemental analysis, FTIR and 1H NMR spectroscopy assured that the amino groups of chitosan reacted with the isothiocyanate groups of the cross-linker producing four new hydrogels namely as BBTU-Cs-1, BBTU-Cs-2, BBTU-Cs-3, and BBTU-Cs-4 according to the increment of their cross-linking content, respectively. SEM showed their porous structures and XRD indicated their amorphous nature. Their swell ability increased with decreasing the medium pH value and with increasing cross-linking density. In comparison with the popular COX inhibitor Celecoxib, these hydrogels showed an inhibition activity towards COX enzymes with selective inhibition towards COX-2. Their inhibition activity could be arranged as follows: Celecoxib > BBTU-Cs-4 > BBTU-Cs-3 > BBTU-Cs-2 > BBTU-Cs-1. BBTU-CS-4 hydrogel exhibited a potent inhibition against COX-2 (IC50 0.42 µg/ml) compared with that observed for the standard Celecoxib (IC50 0.26 µg/ml). BBTU-Cs-4 is more potent against H. pylori compared to the other hydrogels. BBTU-Cs-4 at a concentration of 7.81 µg/ml is able to kill 100% of the H. pylori and exhibits a preferential ability to inhibit 89.35% of COX-2 than COX-1 (0%). These findings make BBTU-Cs-4 a promising anti-H. pylori and selective anti-inflammatory agent.

Shoot aqueous extract of Manihot esculenta Crantz (cassava) acts as a protective agent against paracetamol-induced liver injury.

Manihot esculenta Crantz (Euphorbiaceae), known as cassava, is a widely cultivated plant, considered one of the main sources of food in the tropical and subtropical regions of Africa and Asia. The aim of the present study was the evaluation of the antioxidant and anti-inflammatory effects of cassava shoot aqueous extract (CSAE) on liver injury induced by paracetamol and investigation of its effect on hyperhomocysteinemia. CSAE was administered to male albino rats classified into seven groups: control, treated, and prophylactic groups. A significant reduction in liver enzymes, malondialdehyde, and homocysteine were observed when compared to the paracetamol group, together with an increase in paraoxonase-1. Histopathological and histochemical results indicated that CSAE effectively ameliorate these parameters. Two main flavonol glycosides, quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside, in addition to a minor myricetin 3-O-rutinoside, were identified in CSAE. CSAE showed a therapeutic potential against paracetamol-induced liver injury probably through antioxidant activity of its flavonol glycosides.

Designing, preparation and evaluation of the antimicrobial activity of biomaterials based on chitosan modified with silver nanoparticles.

Chitosan was chemically modified through a four-step procedure. First, the amino groups of chitosan have reacted with benzaldehyde (Derivative 1); second, hydroxyl groups on C6 of Derivative 1 have reacted with epichlorohydrin (Derivative 2); third, the epoxy groups of Derivative 2 have reacted with 4-aminosalicylic acid (Derivative 3); and fourth, benzaldehyde moieties of Derivative 3 have been removed to retrieve the amino groups (Derivative 4). For further modification, three nano-biocomposites were synthesized via impregnating three different concentrations of silver nanoparticles inside Derivative 4. These derivatives and Derivative 4/AgNP composites were structurally identified using elemental analysis, FTIR, XPS, 1H NMR, XRD, SEM, EDS and TEM techniques. These derivatives and Derivative 4/AgNP composites have superior antimicrobial activities than virgin chitosan. Some of them have inhibition zone analogous or superior than the utilized reference drugs. Cytotoxic activity of Derivative 4 and Derivative 4/AgNPs-5 composite indicated that these materials are safe on normal human cells. Accordingly, combinations between chitosan and functional groups derived from the different modifiers in addition to AgNPs within a single structure have extraordinarily enhanced the efficiency of chitosan. It might be deemed as a path to attain promising frameworks which are taken as proper competitors for antimicrobial materials in biomedical fields.

Synthesis and characterization of novel trimellitic anhydride isothiocyanate-cross linked chitosan hydrogels modified with multi-walled carbon nanotubes for enhancement of antimicrobial activity.

Novel trimellitic anhydride isothiocyanate was successfully synthesized and utilized in various concentrations to obtain four novel cross linked chitosan hydrogels H1-H4. Three multi-walled carbon nanotube (MWCNT) biocomposites based on H1 were also prepared. Their structures were proven by elemental analysis, FTIR, XRD, SEM and TEM. They were found to be pH- and temperature-responsive materials. Their swell abilities appreciably depend on their cross linking moiety contents and MWCNTs concentration. They are more potent against Bacillis subtilis, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Geotrichum candidum, Candida albicans, Aspergillus fumigatus, and Syncephalastrum racemosum than chitosan as judged by their greater inhibition zone diameters and their lower minimum inhibitory concentration (MIC) values. Their antimicrobial activities increased with increasing their cross linking moiety contents. They showed a better potency against Gram-positive than Gram-negative bacteria. The hydrogel H4 and H1/MWCNT composites have comparable or even higher activities than the reference bactericides or fungicides against some of tested microbes. Thus, combination between chitosan and the functionalized groups of the incorporated cross linker as well as MWCNTs in one system has efficiently improved the chitosan features. It is a good way for attaining adequate systems as antimicrobial agents that can be taken as promising candidates in biomedical fields.

Novel aminohydrazide cross-linked chitosan filled with multi-walled carbon nanotubes as antimicrobial agents.

Four chemically modified chitosan derivatives 1-4 were designed and synthesized via a series of four reactions; first by reaction with benzaldehyde to protect its amino groups (Derivative 1), second by reaction with epichlorohydrine (Derivative 2), third by reaction with aminobenzhydrazide (Derivative 3), and forth by removing of benzaldehyde to restore the free amino groups on the chitosan (Derivative 4). Two multi-walled carbon nanotube (MWCNT) biocomposites based on Derivative 4 were also prepared. The structure of the prepared derivatives and MWCNT composites was elucidated using elemental analyses, FTIR, XRD, SEM and TEM. The modified chitosan derivatives and MWCNT composites showed better antimicrobial activities than that of chitosan against Enterococcus faecalis, Staphylococcus epidermidis, Escherichia coli, Aspergillus niger, Cryptococcus neoformans and Candida tropicalis as judged by their higher inhibition zone diameters using the agar well diffusion technique. These derivatives and MWCNT composites are more potent against Gram-positive bacteria than against Gram-negative bacteria. The MWCNT composites displayed comparable or even better antimicrobial activities than the reference bactericides or fungicides. Thus, structural modification of chitosan through combination with functionalized moieties and MWCNTs in one system was taken as a way to achieve promising templates for antimicrobial agents and to be appropriate candidates for medical applications.