Synthesis of new Schiff bases bearing 1,2,4-triazole, thiazolidine and chloroazetidine moieties and their pharmacological evaluation.

New compounds based on oxindole moiety were synthesized via the reaction of 5-substitued isatins 1a-e with different nucleophiles such as benzidine, 3,3'-dimethoxybenzidine 2a,b and 2,6-diaminopyridine 3 to afford three different classes of bis-Schiff bases 4a-e, 5a-e and 6a-e, respectively. The structures of the new compounds were elucidated on the basis of their FTIR, 1H NMR, 13C NMR, GC/MS spectral data and elemental analysis. The in vitro antimicrobial activity of the new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration (MIC) against four bacterial and two fungal pathogens and anticancer activities against HELA cervix. The revealed data showed that compound 9d has excellent activity against Gram + ve and Gram -ve bacteria, and compounds 11b presented promising anticancer activity against HELA cervix. [Formula: see text].

Synthesis and in vitro biological evaluation of new heterocycles based on the indole moiety.

New compounds based on the indole moiety were synthesized via the reaction of indole-3-carbinal 1 with different nucleophiles such as 6-aryl-[4-(2-methoxybenzyl)pyridazin-3-yl] hydrazones 2a-c, benzidine, 3,3'-dimethoxybenzidine 4a,b and 2,6-diaminopyridine 6 to afford hydrazine derivatives 3a-c and three different classes of bis-Schiff bases. The structures of the new compounds were elucidated on the basis of their FTIR, (1)H NMR, (13)C NMR spectral data, GC/MS and elemental analysis. The antimicrobial activity of the new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration (MIC) against four pathogenic bacteria and two pathogenic fungi strains. Compound 14b showed excellent activity against Escherichia coli and Klebsiella pneumoniae. Some of the prepared compounds were tested for anti-cancer activity against human cell lines HCT116 (colon), MCF7 (breast) and HELA (cervix). From the results of the in vitro assays, compounds 3a,b, and 18a,c presented promising anti-cancer activity.

Therapeutic applications of sustainable new chitosan derivatives and its nanocomposites: Fabrication and characterization.

Chitosan (CS) is a biologically active biopolymer used in different medical applications due to its biodegradability, biocompatibility, and nontoxicity. Nanotechnology is an exciting and quick developing field in medical applications. Nanoparticles have shown great potential in the treatment of cancer and inflammation. In the present work modification of chitosan and its (Ag, Au, or ZnO) nanocomposites by N-aminophthalimide (NAP) occurred through the reaction with epichlorohydrin (ECH) as a crosslinker in the presence or absence of glutaraldehyde (GA) under different reaction conditions using microwave irradiation to give modified chitosan derivatives CS-2, CS-6, and their nanocomposites. Modified chitosan derivatives were characterized using different tools. CS-2 and CS-6 derivatives displayed enhancement of thermal stability and crystallinity compared to chitosan. Additionally, CS-2, CS-6, and their nanocomposites exhibited improvements in antitumor activity against HeLa cancer cells and enzymatic inhibitory against trypsin and α-chymotrypsin enzymes compared to chitosan. However, CS-2 revealed the highest cell growth inhibition% toward HeLa cells (89.02 ± 1.46 %) and the enzymatic inhibitory toward α-chymotrypsin enzyme (17.13 ± 1.59 %). Furthermore, CS-Au-2 showed the highest enzymatic inhibitory against trypsin enzyme (28.14 ± 1.76 %). These results suggested that the new chitosan derivatives CS-2, CS-6, and their nanocomposites could be a platform for medical applications against HeLa cells, trypsin, and α-chymotrypsin enzymes.

Fabrication and characterization of unique sustain modified chitosan nanoparticles for biomedical applications.

Chitosan (CS) is a biopolymer that offers a wide range in biomedical applications due to its biocompatibility, biodegradability, low toxicity and antimicrobial activity. Syringaldehyde (1) is a naturally occurring organic compound characterized by its use in multiple fields such as pharmaceuticals, food, cosmetics, textiles and biological applications. Herein, development of chitosan derivative with physicochemical and anticancer properties via Schiff base formation from the reaction of chitosan with sustainable eco-friendly syringaldehyde yielded the (CS-1) derivative. Moreover, in the presence of polyethylene glycol diglycidyl ether (PEGDGE) or sodium tripolyphosphate (TPP) as crosslinkers gave chitosan derivatives (CS-2) and (CS-3NPs) respectively. The chemical structures of the new chitosan derivatives were confirmed using different tools. (CS-3NPs) nanoparticle showed improvement in crystallinity, and (CS-2) derivative revealed the highest thermal stability compared to virgin chitosan. The cytotoxicity activity of chitosan and its derivatives were evaluated against HeLa (human cervical carcinoma) and HEp-2 (Human Larynx carcinoma) cell lines. The highest cytotoxicity activity was exhibited by (CS-3NPs) compared to virgin chitosan against HeLa cell growth inhibition and apoptosis of 90.38 ± 1.46% and 30.3% respectively and IC50 of 108.01 ± 3.94 µg/ml. From the above results, it can be concluded that chitosan nanoparticle (CS-3NPs) has good therapeutic value as a potential antitumor agent against the HeLa cancer cell line.

Microwave-assisted synthesis of antimicrobial agents based on pyridazine moiety.

An efficient and simple microwave assisted synthesis of sulfonamide derivatives incorporating the pyridazine moiety has been developed. These sulfonamides were used for the preparation of new heterocyclic compounds via reaction with different reagents using a microwave irradiation technique. The structures of the newly synthesized compounds were confirmed on the basis of FTIR, (1)H and (13)C-NMR, mass spectral techniques and elemental analyses. Some of the new synthesized compounds were assayed for their in vitro antibacterial activity against Gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, Gram-negative bacteria, Escherichia coli and Klebsiella pneumonia and antifungal activity against Aspergillus fumigatus and Candida albicans. Most of the new compounds showed significant antibacterial and antifungal activity.

New potential anti-SARS-CoV-2 and anti-cancer therapies of chitosan derivatives and its nanoparticles: Preparation and characterization.

Chitosan (CS) is a biopolymer and has reactive amine/hydroxyl groups facilitated its modifications. The purpose of this study is improvement of (CS) physicochemical properties and its capabilities as antiviral and antitumor through modification with 1-(2-oxoindolin-3-ylidene)thiosemicarbazide (3A) or 1-(5-fluoro-2-oxoindolin-3-ylidene)thiosemicarbazide (3B) via crosslinking of poly(ethylene glycol)diglycidylether (PEGDGE) using microwave-assisted as green technique gives (CS-I) and (CS-II) derivatives. However, (CS) derivatives nanoparticles (CS-I NPs) and (CS-II NPs) are synthesized via ionic gelation technique using sodium tripolyphosphate (TPP). Structures of new (CS) derivatives are characterized using different tools. The anticancer, antiviral efficiencies and molecular docking of (CS) and its derivatives are assayed. (CS) derivatives and its nanoparticles show enhancement in cell inhibition toward (HepG-2 and MCF-7) cancer cells in comparison with (CS). (CS-II NPs) reveals the lowest IC50 values are 92.70 ± 2.64 µg/mL and 12.64 µ g/mL against (HepG-2) cell and SARS-CoV-2 (COVID-19) respectively and the best binding affinity toward corona virus protease receptor (PDB ID 6LU7) -5.71 kcal / mol. Furthermore, (CS-I NPs) shows the lowest cell viability% 14.31 ± 1.48 % and the best binding affinity -9.98 kcal/moL against (MCF-7) cell and receptor (PDB ID 1Z11) respectively. Results of this study demonstrated that (CS) derivatives and its nanoparticles could be potentially employed for biomedical applications.

New sustainable antimicrobial chitosan hydrogels based on sulfonamides and its nanocomposites: Fabrication and characterization.

Chitosan (Ch), a linear cationic biopolymer, has broad medical applications. In this paper, new sustainable hydrogels (Ch-3, Ch-5a, Ch-5b) based on chitosan/sulfonamide derivatives 2-chloro-N-(4-sulfamoylphenethyl) acetamide (3) and/or 5-[(4-sulfamoylphenethyl) carbamoyl] isobenzofuran-1,3-dione (5) were prepared. Hydrogels (Ch-3, Ch-5a, Ch-5b) were loaded (Au, Ag, ZnO) NPs to form its nanocomposites to improve the antimicrobial efficacy of chitosan. The structures of hydrogels and its nanocomposites were characterized using different tools. All hydrogels displayed irregular surface morphology in SEM, however hydrogel (Ch-5a) revealed the highest crystallinity. The highest thermal stability was shown by hydrogel (Ch-5b) compared to chitosan. The nanocomposites represented nanoparticle sizes <100 nm. Antimicrobial activity was assayed for hydrogels using disc diffusion method exhibited great inhibition growth of bacteria compared to chitosan against S. aureus, B. subtilis and S. epidermidis as Gram-positive, E. coli, Proteus, and K. pneumonia as Gram-negative and antifungal activity against Aspergillus Niger and Candida. Hydrogel (Ch-5b) and nanocomposite hydrogel (Ch-3/Ag NPs) showed higher colony forming unit (CFU) and reduction% against S. aureus and E. coli reaching 97.96 % and 89.50 % respectively in comparison with 74.56 % and 40.30 % for chitosan respectively. Overall, fabricated hydrogels and its nanocomposites enhanced the biological activity of chitosan and it can be potential candidates as antimicrobial drugs.

Antiproliferative effects of metal complexes of new isatin hydrazones against HCT116, MCF7 and HELA tumour cell lines.

New hydrazone ligands (HL) derived from 5-substituted isatins and 1-(4-(2-methoxybenzyl)-6-arylpyridazin-3-yl)hydrazines and its complexes with Co(II) and Cu(II) were synthesized. The new hydrazones and their complexes were characterized by means of elemental, spectral analyses and magnetic studies. Primary cytotoxicity evaluation of HL 5a and the new complexes showed that these complexes could act as anticancer agents since they reduced the growth of samples of human tumour cell lines (HCT116((Colon)), MCF7((Breast)) and HELA((Cervix))) to ≤18.5 µg/mL for the new complexes.

Synthesis, characterization and in vitro antimicrobial evaluation of new compounds incorporating oxindole nucleus.

New compounds incorporating with the oxindole nucleus were synthesized via the reaction of substituted isatins [5-methyl-, 5-chloro- and 1-hydroxymethyl isatins] with different nucleophiles. The structures of the newly compounds were elucidated on the basis of FTIR, (1)H NMR, (13)CMR spectral data, GC/MS and chemical analysis. Investigation of antimicrobial activity of the new compounds was evaluated using broth dilution technique in terms of minimal inhibitory concentration (MIC) count against four pathogenic bacteria and two pathogenic fungi. Most of the new compounds are significantly active against bacteria and fungi. MIC showed that compound (4a) possesses higher effect on Gram-positive bacteria Bacillus cereus than the selected antibacterial agent sulphamethoxazole, whereas compound (11c) possesses more activity against Gram-negative bacteria Shigella dysenterie.

Sustainable antimicrobial modified chitosan and its nanoparticles hydrogels: Synthesis and characterization.

The target of the present study is the development of sustainable chitosan and chitosan nanoparticles-based heterocyclic compound hydrogels with antimicrobial properties. Sustainable antimicrobial new modified chitosan hydrogel (CS-3) was synthesized by the reaction of chitosan (CS) with 2-([4-[(1, 3-dioxoisoindolin-2-ylimino) methyl] phenyl] methyleneamino) isoindoline-1, 3-dione (3) via ring opening of cyclic imide moiety in compound (3). However, the modified chitosan nanoparticles hydrogel (CS-3 NPs) were prepared in-situ by an ionotropic gelation technique using sodium tripolyphosphate (TPP) as the cross-linking agent. The prepared hydrogels were characterized by FTIR, SEM, TEM, TGA, DSC and elemental analysis. The hydrogels were tested versus eight pathogenic strains of Gram +ve and Gram -ve bacteria and two fungi. The results revealed that hydrogels (CS-3) and (CS-3 NPs) showed higher antimicrobial activities than virgin (CS) and (CS-NPs). However, hydrogel (CS-3 NPs) showed the highest Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) especially with Gram +ve bacteria (S. pyogenes) at 19.5 and 39 µg/ml compared to the standard antibiotic Ciprofloxacin at 19 and 38 µg/ml respectively.

New heterocycle modified chitosan adsorbent for metal ions (II) removal from aqueous systems.

A new hydrogel based on a modified chitosan CS-B was synthesized and evaluated for its metal ion removal from aqueous systems. The CS-B hydrogel was prepared through modification of chitosan with 4-((1, 3-dioxoisoindolin-2-ylimino) methyl) benzaldehyde as a heterocyclic component. The new hydrogel was analyzed by diverse techniques such as FTIR, XRD, TGA, SEM, and swelling tests. The adsorption capacity of CS-B for metal ions Co(2+), Hg(2+), Cu(2+), Zn(2+), and Pb(2+) from aqueous systems at different pH values showed various levels of efficiency. The metal ion uptake data over a range of pH values for Co(2+) and Hg(2+) showed the highest adsorption capacity while Cu(2+), Zn(2+), and Pb(2+) showed moderate adsorption capacity. Selective metal ion efficiency was highest for Co(2+) and lowest for Hg(2+) in their binary mixture.