Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a (DP)-induced AR mouse model.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties.

New cell cycle checkpoint pathways regulators with 2-Oxo-indoline scaffold as potential anticancer agents: Design, synthesis, biological activities and in silico studies.

3-Arylidene-2-oxo-indoline derivatives are at the heart of a wide range of clinically, medicinally and biologically important compounds among the 2-oxo-indolines. A number of 3-arylidene-2-oxo-indolines have been approved for clinical application. Accordingly, the current work describes the structural based design of 3-arylidene-2-oxindole derivatives through docking of their structures in the active site of CDK2 as one of the dominant enzyme checkpoints.

Inversion kinetics of some / 3-(benzylidene)-2-oxo-indoline derivatives and their CDK2 docking studies.

The structure-based design of some CDK2 inhibitors with a 3-(benzylidene)indolin-2-one scaffold as potential anticancer agents was realized. Target compounds were obtained as / mixtures and were resolved to corresponding - and -diastereomers. studies using MOE 2019.

Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents.

In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s).

Pharmacokinetic studies of naproxen amides of some amino acid esters with promising colorectal cancer chemopreventive activity.

Naproxen (nap) is belonging to Non-steriodal anti-inflammatory drugs (NSAIDs) group of drugs that characterized by their free carboxylic group. The therapeutic activity of nap is usually accompanied by GI untoward side effects. Recently synthesized naproxen amides of some amino acid esters prodrugs to mask the free carboxylic group were reported.

Synthesis, characterization and pharmacological evaluation of certain enzymatically cleavable NSAIDs amide prodrugs.

The presence of free carboxylic acid group in majority of non-steroidal anti-inflammatory drug (NSAIDs) is responsible from GI irritation. Coupling of the appropriate NSAIDs (diclofenac, naproxen, dexibuprofen and meclofenamic acid) 1-4, respectively with the appropriate amino acid ester 5 using dicyclohexylcarbodiimide afforded prodrugs 6-13. The structures of the prodrugs were verified based on spectral data.

Synthesis and anti-mycobacterial activity of 4-(4-phenyl-1H-1,2,3-triazol-1-yl)salicylhydrazones: revitalizing an old drug.

The antitubercular drug; para-aminosalicylic acid (PAS) was used as the core scaffold for the design of a series of 1H-1,2,3-triazolylsalicylhydrazones upon coupling with triazole and arylhydrazone moietis to furnish a single molecular architecture. The obtained derivatives were screened against Mycobacterium tuberculosis H37Rv revealing good to high activity for the active compounds (MIC values of 0.39-1.

Novel non-cyclooxygenase inhibitory derivatives of naproxen for colorectal cancer chemoprevention.

A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with showing IC of 11.4 μM (two orders of magnitude more potent than naproxen).

Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity.

Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines.

Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative activity.

Background: Cancer is one of the most dreaded diseases and it is a leading cause of mankind death worldwide. Recent reports documented a remarkable antiproliferative activity of isatin nucleus against various cancer cell lines. The current work describes the antiproliferative activity of Schiff bases of combinatorial mixtures of the isatin derivatives M1-M22 as well as the individual compounds 1-11(A-K) of these combinatorial mixtures.

3,5-disubstituted thiadiazine-2-thiones: new cell-cycle inhibitors.

Two series, a and b, of 3-cyclopentyl or (3-cyclohexyl)-5-substituted-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTT) 2a-9a and 3b, 4b, 6b-9b, were synthesized to develop new cell cycle inhibitors. Variable and promising in vitro antiproliferative activities were shown with the synthesized THTT derivatives. Compound 5a with a 5-cyclopentyl group on position-3 and a glutamine residue on position-5 of the THTT moiety showed maximum activity (IC(50) = 8.

(Z)-Ethyl 2-cyano-2-{2-[5,6-dimethyl-4-(thio-phen-2-yl)-1H-pyrazolo-[3,4-b]pyridin-3-yl]hydrazinylidene}acetate.

In the title compound, C(17)H(16)N(6)O(2)S, an intra-molecular N-H⋯O inter-action generates an S(6) ring. The pyridine ring makes a dihedral angle of 71.38 (11)° with the thio-phene ring.

Microwave-assisted solution-phase synthesis and DART-mass spectrometric monitoring of a combinatorial library of indolin-2,3-dione schiff bases with potential antimycobacterial activity.

A combinatorial library composed of eleven hydrazides A-K and eleven indolin-1,2-dione derivatives 1-11 has been designed to formally generate sublibraries of 22 mixtures, M(1)-M(22) comprising of 121 Schiff bases, A-K(1-11). The designed library has been synthesized by the solution-phase method and microwave-assisted synthetic techniques. The formation of individual compounds of each mixture was confirmed by Direct Analysis in Real Time (DART) as ionization technique connected to an Ion Trap as a mass detector.

Schiff bases of indoline-2,3-dione (isatin) derivatives and nalidixic acid carbohydrazide, synthesis, antitubercular activity and pharmacophoric model building.

Tuberculosis (TB) remains among the world's great public health challenges. Worldwide resurgence of TB is due to two major problems: the AIDS epidemic, which started in the mid-1980s, and the outbreak of multidrug resistant (MDR) TB. Thus, there is an urgent need for anti-TB drugs with enhanced activity against MDR strains.

Cell cycle disruption and apoptotic activity of 3-aminothiazolo[3,2-a]benzimidazole-2-carbonitrile and its homologues.

3-aminothiazolo[3,2-a]benzimidazole-2-carbonitrile (2) was prepared and upon hydrolysis using concentrated sulfuric acid or phosphoric acid resulted in the corresponding 3-aminothiazolo[3,2-a]benzimidazole-2-carboxamide derivative (3). Cyclization of the 2 using acetic anhydride or formic acid gave the corresponding pyrimido[4',5':4,5]thiazolo[3,2-a]benzimidazol-4(3H)-one (5) in good yields. Acetylation of 2 with acetic anhydride in pyridine afforded N-acetylaminothiazolo[3,2-a]benzimidazole-2-carbonitrile (6).

Selective Spectrophotometric and Spectrofluorometric Methods for the Determination of Amantadine Hydrochloride in Capsules and Plasma via Derivatization with 1,2-Naphthoquinone-4-sulphonate.

New selective and sensitive spectrophotometric and spectrofluorometric methods have been developed and validated for the determination of amantadine hydrochloride (AMD) in capsules and plasma. The methods were based on the condensation of AMD with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product. The spectrophotometric method involved the measurement of the colored product at 460 nm.

Pharmacophoric model building for antitubercular activity of the individual Schiff bases of small combinatorial library.

Synthesis and evaluation of anti-TB activity of individual compounds of Schiff bases combinatorial library were done against Mycobacterium tuberculosis H(37)Rv at a single concentration of 6.25mug/mL according to the protocol of TAACF. Compounds 2C and 3D produced 99% inhibitory activity on the investigated organism, while the other tested compounds showed lower activity ranging from 35 to 84%.

(Z)-3-Hydrazinyl-idene-1-phenyl-indolin-2-one.

The indoline fused-ring system of the title Schiff base, C(14)H(11)N(3)O, is planar (r.m.s.

A highly sensitive enzyme immunoassay for evaluation of 2'-deoxycytidine plasma level as a prognostic marker for breast cancer chemotherapy.

A highly sensitive competitive enzyme immunoassay (EIA) has been developed and validated for the determination of the plasma level of 2'-deoxycytidine (dCyd), the potential prognostic marker for breast cancer chemotherapy. This assay employed a monoclonal antibody that recognizes dCyd with a high specificity, and 5'-succinyl-dCyd (5'sdCyd) conjugate of bovine serum albumin (5'sdCyd-BSA) immobilized onto microplate wells as a solid phase. The assay involved a competitive binding reaction between dCyd, in plasma sample, and the immobilized 5'sdCyd-BSA for the binding sites of the anti-dCyd antibody.

Pre- and post-initiation chemoprevention activity of 2-alkyl/aryl selenazolidine-4(R)-carboxylic acids against tobacco-derived nitrosamine (NNK)-induced lung tumors in the A/J mouse.

The efficacy of a series of 2-aryl/alkyl selenazolidine-4(R)-carboxylic acids (SCAs) in reducing NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung adenomas in female A/J mice, a model for tobacco-related lung tumorigenesis, has been investigated. With selenazolidines in the diet for 1 month prior to carcinogen administration and during the subsequent 4 months of tumor development, 2-butylSCA, 2-cyclohexylSCA, 2-phenylSCA and 2-oxoSCA were chemopreventive, significantly reducing mean lung tumor numbers from the 10.9 of unsupplemented controls to 4.