Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The ...structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance. The results of scanning electron microscopy, thermal gravimetric analysis, and X-ray diffraction indicated that the morphology changed to a porous nature, the thermal stability decreased, and the crystallinity increased in the DMS-CH derivative compared to chitosan, respectively. The degree of substitution was calculated from the elemental analysis data and was found to be moderate (42%). The modified chitosan exhibited enhanced antimicrobial properties at low concentrations, with a minimum inhibitory concentration (MIC) of 50 µg/mL observed for B. subtilis and P. aeruginosa, and a value of 25 µg/mL for S. aureus, E. coli, and C. albicans. In the case of native chitosan, the MIC values doubled or more, with 50 µg/mL recorded for E. coli and C. albicans and 100 μg/mL recorded for B. subtilis, S. aureus, and P. aeruginosa. Furthermore, toxicological examinations conducted on MCF-7 (breast adenocarcinoma) cell lines demonstrated that DMS-CH exhibited greater toxicity (IC50 = 225.47 μg/mL) than pure CH, while still maintaining significant safety limits against normal lung fibroblasts (WI-38). Collectively, these results suggest the potential use of the newly modified chitosan in biomedical applications.
The emergence of multidrug-resistant microbes and the propagation of cancer cells are global health issues. The unique properties of chitosan and its derivatives make it an important candidate for ...therapeutic applications. Herein, a new thiadiazole derivative, 4-((5-(butylthio)-1,3,4-thiadiazol-2-yl) amino)-4-oxo butanoic acid (BuTD-COOH) was synthesized and used to modify the chitosan through amide linkages, forming a new thiadiazole chitosan derivative (BuTD-CH). The formation of thiadiazole and the chitosan derivative was confirmed by FT-IR,
H/
C-NMR, GC-MS, TGA, Elemental analysis, and XPS. The BuTD-CH showed a high antimicrobial effect against human pathogens Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Candida albicans with low MIC values of 25-50 μg ml
compared to unmodified chitosan. The in-vitro cytotoxicity of BuTD-CH was evaluated against two cancer cell lines (MCF-7 and HepG2) and one normal cell (HFB4) using the MTT method. The newly synthesized derivatives showed high efficacy against cancerous cells and targeted them at low concentrations (IC
was 178.9 ± 9.1 and 147.8 ± 10.5 μg ml
for MCF-7 and HepG2, respectively) compared with normal HFB4 cells (IC
was 335.7 ± 11.4 μg ml
). Thus, low concentrations of newly synthesized BuTD-CH could be safely used as an antimicrobial and pharmacological agent for inhibiting the growth of human pathogenic microbes and hepatocellular and adenocarcinoma therapy.
This study aims to synthesize and evaluate the corrosion inhibition properties of three newly prepared organic compounds based on benzohquinoline hydrazone derivatives. The compounds structure were ...characterised using FTIR, 1H-NMR, 13C-NMR and Mass spectroscopy. Electrochemical methods, including Potentiodynamic Polarization (PP), Electrochemical Frequency Modulation (EFM), and Electrochemical Impedance Spectroscopy (EIS) were employed to evaluate the compounds as corrosion inhibitors in HCl (1.0 M) for carbon steel (CS). Additionally, surface examination techniques such as scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to investigate the surface morphology and elemental composition of the CS before and after exposure to the synthesized compounds. The electrochemical measurements showed that compound VII achieved corrosion inhibition efficiency. SEM and EDX analysis further confirmed the creation of a passive film on the CS surface. These findings demonstrated the potential of benzohquinoline hydrazone derivatives as effective organic corrosion inhibitors for CS in aggressive solution.
Recently, chitosan and its derivatives have been gaining more attention due to their high integration into various biomedical applications. Herein, a new chitosan derivative was prepared by linking ...the chitosan (Cs) with a novel heterocyclic compound, Benzoimidazolyl-thiadiazole (BzimTD) to form Cs-BzimTD. The synthesis of the new chitosan derivative was confirmed by Fourier-Transform Infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR), thermogravimetric (TGA-DTG) analysis, elemental analysis, and UV–Visible spectrophotometer. Data showed the high efficacy of functionalized Cs-BzimTD to inhibit the growth of pathogenic microbes, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with inhibition zones of 15.3 ± 0.6 – 9.2 ± 0.3 mm. Also, Cs-BzimTD was applied in a topical gel formulation by using two different polymers, Carbopol 940 (CP) and Carboxymethyl Cellulose (CMC) to form three gel formulations: Cs-BzimTD-CP, Cs-BzimTD-CMC, and Cs-BzimTD-CP-CMC. The new gels were checked for physical appearance, viscosity, Cs-BzimTD release, pH, spread-ability, and drug content. The results showed that all formulations were clear, transparent, and homogeneous with non-irritant pH values for skin (6.4 – 6.8). The spread-ability was found in the range of 7.1 – 9.4 g.cm/s. The Cs-BzimTD-CP formula showed the maximal Cs-BzimTD content percentage (86.5%) and the Cs-BzimTD release varied from 89.9 to 81.6% after 8 h depending on the gel formulation, with a maximum release achieved for Cs-BzimTD-CMC.
This work reports the synthesis of a new pyrazole derivative by reacting 5-amino-1,3-diphenyl pyrazole with succinic anhydride and bearing the product chemically on the chitosan chains via amide ...linkage to achieve a new chitosan derivative (DPPS-CH). The prepared chitosan derivative was analyzed by IR, NMR, elemental analysis, XRD, TGA-DTG, and SEM. As compared with chitosan, DPPS-CH showed an amorphous and porous structure. Coats-Redfern results showed that the thermal activation energy for the first decomposition of DPPS-CH is 43.72 KJ mol−1 lower than that required for chitosan (88.32 KJ mol−1), indicating the accelerating effect of DPPS on the thermal decomposition of DPPS-CH. The DPPS-CH manifested a powerful wide spectrum antimicrobial potential against pathogenic gram-positive and gram-negative bacteria and Candida albicans at minute concentrations (MIC = 50 μg mL−1) compared to chitosan (MIC = 100 μg mL−1). The MTT assay proved the toxic properties of DPPS-CH against a cancer cell line (MCF-7) at a minute concentration (IC50 = 15.14 μg mL−1) while affecting normal cells (WI-38) at seven times this concentration (IC50 = 107.8 μg mL−1). According to the current findings, the chitosan derivative developed in this work appears to be a promising material for use in biological domains.
•New diphenyl pyrazole-succinic acid derivative, DPPS, was prepared.•New chitosan derivative bearing the new pyrazole moiety, DPPS-CH, was reported.•DPPS-CH was analyzed in terms of IR, NMR, TGA-DTG, XRD, and SEM.•DPPS-CH showed enhanced antimicrobial effect.•The toxic properties of DPPS-CH against cancer cell line (MCF-7) were proved.
Herein, two new polymers designated as Cs-EATT and Cs-BATT have been synthesized via linking the chitosan with the synthesized 1,3,4-thiadiazole compounds. They were characterized using
1
H,
13
...C-NMR, FT-IR, TGA, Elemental analysis, Mass spectrum, and UV–vis spectrophotometer. The synthesized polymers exhibit high activity to control the growth of pathogenic bacteria (
S. aureus
,
B. subtilis
,
E. coli,
and
P. aeruginosa
), and unicellular fungi (
C. albicans
). The MIC values were in the range of 25–100 µg mL
–1
for Cs-EATT and 25–200 µg mL
–1
for Cs-BATT with varied clear zones. The new polymers were mixed with three film-forming agents: polyvinyl alcohol, hydroxyethyl cellulose, and carboxymethyl cellulose to form six film dressings designated as E1, E2, and E3 for Cs-EATT, and B1, B2, and B3 for Cs-BATT, respectively. The evaluation of film dressings showed that the formed films had transparency, uniformity, homogeneity, elasticity, and non-irritation pH values for skin within the normal range. The maximum percentages of Cs-E/B-ATT content were recorded for film dressings E2 and B2, with values of 92.5% and 94.9%, respectively. Also, the release percentages varied according to film dressing formulation, with values in the ranges of 83.88–93.2% for Cs-EATT and (87.7–97.35%) for Cs-EATT after 9 h.
Protein kinases orchestrate diverse cellular functions; however, their dysregulation is linked to metabolic dysfunctions, associated with many diseases, including cancer. Mitogen-Activated Protein ...(MAP) kinase is a notoriously oncogenic signaling pathway in human malignancies, where the extracellular signal-regulated kinases (ERK1/2) are focal serine/threonine kinases in the MAP kinase module with numerous cytosolic and nuclear mitogenic effector proteins. Subsequently, hampering the ERK kinase activity by small molecule inhibitors is a robust strategy to control the malignancies with aberrant MAP kinase signaling cascades. Consequently, new heterocyclic compounds, containing a sulfonamide moiety, were rationally designed, aided by the molecular docking of the starting reactant 1-(4-((4-methylpiperidin-1-yl)sulfonyl)phenyl)ethan-1-one (
) at the ATP binding pocket of the ERK kinase domain, which was relying on the molecular extension tactic. The identities of the synthesized compounds (
-
) were proven by their spectral data and elemental analysis. The target compounds exhibited pronounced anti-proliferative activities against the MCF-7, HepG-2, and HCT-116 cancerous cell lines with potencies reaching a 2.96 μM for the most active compound (
). Moreover, compounds
,
,
,
, and
displayed a significant G2/M phase arrest and induction of the apoptosis, which was confirmed by the cell cycle analysis and the flow cytometry. Thus, the molecular extension of a small fragment bounded at the ERK kinase domain is a valid tactic for the rational synthesis of the ERK inhibitors to control various human malignancies.
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•Thirteen compounds of new N-sulfonylpiperidines were designed and synthesized.•Cytotoxic activities were evaluated against HCT-116, HepG-2, and MCF-7 cell lines.•In vitro VEGFR-2 ...inhibition was evaluated.•Cell cycle and apoptosis analyses were performed.•Molecular docking studies were carried out.
A new panel of N-sulfonylpiperidine derivatives has been designed and synthesized as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. Anti-proliferative activities of the synthesized members were tested against colorectal carcinoma (HCT-116), hepatocellular carcinoma (HepG-2), and breast cancer (MCF-7) cell lines. Compounds 3a, 4, 8, and 9 showed the highest activities against the tested cell lines. In particular, compound 8 showed excellent activities against HCT-116, HepG-2, and MCF-7 with IC50 values of 3.94, 3.76, and 4.43 μM, respectively. Such IC50 values are comparable to vinblastine (IC50 = 3.21, 7.35, 5.83 μM, respectively) and doxorubicin (IC50 = 6.74, 7.52, 8.19 μM, respectively). In vitro VEGFR-2 inhibitory activity of the most promising molecules (3a, 4, 8, and 9) indicated that compound 8 is the highest VEGFR-2 inhibitor with an IC50 of 0.0554 μM, compared to sorafenib (IC50 = 0.0416 μM). The most promising candidates (3a, 4, 8, and 9) were subjected to flow cytometry analyses to assess their effects on the cell cycle behavior and the apoptotic power against the three tested cell lines (HCT-116, HepG-2, and MCF-7). The tested compound arrested the tumor cells at both the G2/M and Pre-G1 phases. In addition, compound 9 was proved as the most effective apoptotic inducer among the tested compounds against the tested cells. Molecular docking studies against VEGFR-2 (PDB ID: 2OH4) revealed good binding modes of the synthesized compound similar to that of sorafenib. Computational investigation of ADMET parameters revealed the drug-likeness of the synthesized compounds.
This work presents the synthesis and
, and
analyses of new thiadiazole derivatives that are designed to mimic the pharmacophoric characteristics of vascular endothelial growth factor receptor-2 ...(VEGFR-2) inhibitors. A comprehensive evaluation of the inhibitory properties of the synthesized thiadiazole derivatives against the cancer cell lines MCF-7 and HepG2 identified several auspicious candidates. Among them, compound 14 showed remarkably low IC
values of 0.04 μM and 0.18 μM against MCF-7 and HepG2, respectively. VEGFR-2 inhibitory evaluation of compound 14 revealed a promising IC
value in the nanomolar range (103 nM). Further examination of the cell cycle revealed that compound 14 has the ability to stop the progression of the cell cycle in MCF-7 cells
G0-G1 phase arrest. Interestingly, compound 14 also demonstrated a noteworthy pro-apoptotic effect in MCF-7 cells, with notable increases in early apoptosis (16.53%) and late apoptosis (29.57%), along with a slight increase in the population of necrotic cells (5.95%). Furthermore, compound 14 showed a significant drop in MCF-7 cells' ability to migrate and heal wounds. Additionally, compound 14 promoted apoptosis by boosting BAX (6-fold) while lowering Bcl-2 (6.2-fold). The binding affinities of the synthesized candidates to their target (VEGFR-2) were confirmed by computational investigations, including molecular docking, principal component analysis of trajectories (PCAT), and molecular dynamics (MD) simulations. Additionally, compound 14's stability and reactivity were investigated using density functional theory (DFT). These thorough results highlight compound 14's potential as a lead contender for additional research in the creation of anticancer drugs that target VEGFR-2. This work establishes a foundation for promising thiadiazole derivatives for future therapeutic developments in anticancer- and angiogenesis-related scientific fields.
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