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Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug–cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects. [ABSTRACT FROM AUTHOR]

The synthesis of a new xanthine nitric oxide donor (TSP-81) has been discussed. The designed compound includes two structural moieties - theophylline (1,3-dimethylxanthine) and acetaminophen (4-hydroxyacetanilide) linked by the nitric oxide donor alkyl chain as a spacer. The compound has been characterized by microanalysis (CHN), 1H-NMR, 13C-NMR, FT-IR, UV-vis, TG and DTG. The thermal behaviour showed that TSP-81 melts with decomposition, in four steps, the most important ones being the 2nd one (the registered weight loss being 17.6 %) and the 3rd one (with a registered weight loss of 30.4 %). The toxicity degree, the anti-inflammatory effect and the ability of releasing nitric oxide of the TSP-81 have also been evaluated. The biological assays established that TSP-81 exhibits enhanced biological properties such as lower toxicity and higher anti-inflammatory effect in reference with theophylline and acetaminophen, the drugs used as parents molecules. The TSP-81 is approximately 2 times more active than theophylline and 4 times more active than acetaminophen in reducing cotton pellet-granuloma formation. Furthermore, the release of nitric oxide (NO) appears to have an important contribution to enhancing the anti-inflammatory effect.

The objective of this study was to develop new films based on chitosan functionalized with sulfonamide drugs (sulfametoxydiazine, sulfadiazine, sulfadimetho-xine, sulfamethoxazol, sulfamerazine, sulfizoxazol) in order to enhance the biological effects of chitosan. The morphology and physical properties of functionalized chitosan films as well the antioxidant effects of sulfonamide-chitosan derivatives were investigated. The chitosan-derivative films showed a rough surface and hydrophilic properties, which are very important features for their use as a wound dressing. The film based on chitosan-sulfisoxazol (CS-S6) showed the highest swelling ratio (197%) and the highest biodegradation rate (63.04%) in comparison to chitosan film for which the swelling ratio was 190% and biodegradation rate was only 10%. Referring to the antioxidant effects the most active was chitosan-sulfamerazine (CS-S5) which was 8.3 times more active than chitosan related to DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging ability. This compound showed also a good ferric reducing power and improved total antioxidant capacity. [ABSTRACT FROM AUTHOR]

New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the total antioxidant activity, the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be involved in many pathological events like diabetes mellitus, neurodegenerative diseases, cancer, infections and more recently, in inflammation. It is known that overproduction of free radicals may initiate and amplify the inflammatory process via upregulation of genes involved in the production of proinflammatory cytokines and adhesion molecules. The chemical modulation of acyl hydrazones of ibuprofen 3a-l through cyclization to the corresponding thiazolidine-4-ones 4a-n led to increased antioxidant potential, as all thiazolidine-4-ones were more active than their parent acyl hydrazones and also ibuprofen. The most active compounds are the thiazolidine-4-ones 4e, m, which showed the highest DPPH radical scavenging ability, their activity being comparable with vitamin E. [ABSTRACT FROM AUTHOR]

In the search of improving the pharmacological properties of theophylline in the field of the bronchodilatory action, five new theophylline derivatives have been synthesized, starting from 8-substituted theophylline and a paracetamol derivative. The variety of radicals used as substituents, such as hydrogen, bromo, nitro, pyrrolidinyl, piperidinyl and morpholinyl has lead to different behavior of the obtained compounds as concerning the tracheal smooth muscle relaxation. The chemical structure was investigated by means of FTIR and 1H-NMR spectroscopy. The optimized geometry and the electro-optical characteristics have been determined using quantum chemical calculations in AM1 approximation. The infrared spectral characteristics were compared to those obtained through computational approaches. The energetic characteristics of the compounds under study are relevant for both their chemical reactivity and biological action. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug that mainly works by reducing insulin resistance, while curcumin (Cur) is a powerful antioxidant with an important hypoglycemic effect. Both drugs are associated with several drawbacks, such as reduced bioavailability and a short half-life time (Pio), as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, new co-delivery (Pio and Cur) chitosan-based nanoparticles (CS-Pio-Cur NPs) were developed and compared with simple NPs (CS-Pio/CS-Cur NPs). The NPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). In addition, the entrapment efficiency (EE) and loading capacity (LC), as well as the release profile, of the APIs (Pio and Cur) from the CS-APIs NPs in simulated fluids (SGF, SIF, and SCF) were also assessed. All the CS-APIs NPs presented a small particle size (PS) (211.6-337.4 nm), a proper polydispersity index (PI) (0.104 and 0.289), and a positive zeta potential (ZP) (21.83 mV-32.64 mV). Based on the TEM results, an amorphous state could be attributed to the CA-APIs NPs, and the TEM analysis showed a spherical shape with a nanometric size for the CS-Pio-Cur NPs. The FT-IR spectroscopy supported the successful loading of the APIs into the CS matrix and proved some interactions between the APIs and CS. The CS-Pio-Cur NPs presented increased or similar EE (85.76% ± 4.89 for Cur; 92.16% ± 3.79 for Pio) and LC% (23.40% ± 1.62 for Cur; 10.14% ± 0.98 for Pio) values in comparison with simple NPs, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 22.31% ± 0.94), and CS-Pio NPs (EE = 93.67% ± 0.89; LC = 11.24% ± 0.17), respectively. Finally, based on the release profile results, it can be appreciated that the developed co-delivery nanosystem, CS-Pio-Cur NPs, assures a controlled and prolonged release of Pio and Cur from the polymer matrix along the GI tract.

The first access to 3,5-disubstituted imidazo[1,2- d ][1,2,4]thiadiazole derivatives is reported. The series were generated from 2-mercaptoimidazole, which afforded the key intermediate bearing two functional positions. The S N Ar reactivity toward tosyl release at the C-3 position was investigated and a regioselective electrophilic iodination in C-5 position was performed to allow a novel C-C bond using Suzuki-Miyaura reaction. Palladium-catalyzed cross-coupling conditions were optimized. A representative library of various boronic acids was employed to establish the scope and limitations of the method. To complete this methodological study, the influence of the nature of the C-3 imidazo[1,2- d ][1,2,4]thiadiazole substitutions on the arylation in C-5 was investigated., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

In order to obtain new compounds with antitumoural action the N-(meta-acylaminobenzoyl)-alpha-acylaminobenzoyl)-alpha-aminoacids 4-9 were prepared. These compounds were subsequently converted into the corresponding Delta(2)-oxazolin-5-ones 10-15, which in turn were submitted to a ring opening reaction with di-(beta-chloroethyl)amine to afford the peptide supported N-mustards 16-21, which showed low toxicity and cytostatic activity similar to that of sarcolisine against the Ehrlich ascite and Walker 253 carcinosarcoma.