A series of 1,2,4-triazole-3-acetamides 3a-b, 1-acylated-1,2,4-triazole-3- acetamides 4a-b, ethyl 5-(2-substitutedacetamido)-1H-1,2,4-triazole-3-acetates 6, 7, 8, ethyl 1- substituted (carbamoyl and thiocarbamoyl)-5-amino-1H-1,2,4-triazole-3-acetates 9a-j and ethyl 5-(3(4-chlorophenyl)ureido-1H-1,2,4-triazol-3-acetate 10 were synthesized. The obtained compounds were evaluated for their anti-inflammatory. Most of the tested compounds exhibited significant anti-inflammatory activities with compounds 9a-j were better than indomethacin. None of the tested compounds showed significant antitumor activity. Finally docking of selected compounds was performed to COX-2 and COX-1 enzymes in order to rationalize the obtained anti-inflammatory results and to predict the selectivity of the synthesized compounds.

The formation of a colored charge-transfer (CT) complex between atorvastatin calcium (ATR-Ca) as a n-electron donor and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for determination of ATR-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwellplate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9995) was found between the absorbance and the concentration of ATR-Ca in the range of 10-150 μg/well. The limits of detection and quantitation were 5.3 and 15.8 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ATR-Ca in its combined formulations. The assay was successfully applied to the analysis of ATR-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ATR-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposures of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50-fold. Although the proposed assay was validated for ATR-Ca, however, the same methodology could be used for any electron-donating analyte for which a CT reaction can be performed.

In research for promising antibacterial and antifungal compounds, a series of 2-aryl 3-[1,2,4]triazol-5-yl 4-thiazolidinones 1 were synthesized by a domino reaction of 5-amino-1H-[1,2,4]triazoles 3, aromatic aldehydes, and -mercaptoacids in boiling toluene in the presence of molecular sieves 4 A°. Of the twenty novel 3-[1,2,4]triazol-5-yl 4-thiazolidinone derivatives, four compounds 2-benzo[d][1,3]dioxol-6-yl-3-[(3-morpholin-4-yl)-1H-1,2,4-triazol-5-yl)]-1,3-thiazolidin-4-one (1i), 2-(4-chlorophenyl)-5-methyl-3-[3-(4-methylpiperazin-1-yl)-1H-1,2,4-triazol-5-yl]-1,3-thiazolidin-4-one (1p), 2-benzo[d][1,3]dioxol-6-yl-3-[3-(4-methylpiperazin-1-yl)-1H-1,2,4-triazol-5-yl]-1,3-thiazolidin-4-one (1s), 2-benzo[d][1,3]dioxol-6-yl-5-methyl-3-[3-(4-methylpiperazin-1-yl)-1H-1,2,4-triazol-5-yl]-1,3-thiazolidin-4-one (1t) exhibited MICs of 4 mg/mL or less versus Mycobacterium tuberculosis. Moreover, these compounds were screened against Candida albicans. Compounds 1p, 1s gave MICs of 1 mg/mL or less, and were fungicidal. Finally, compound 1s was evaluated against an expanded fungal panel and showed good activity against Cryptococcus neoformans. In addition, compound 1s also appeared to be fungicidal against Aspergillus arrhizus, with MIC 1 mg/mL.

A series of pyrazine-2-carboxylic acid hydrazide derivatives were synthesized and screened for their activity against Mycobacterium tuberculosis. The results show that pyrazine-2-carboxylic acid hydrazide-hydrazone derivatives 3a-l were less active than pyrazinamide. In contrast, the N4-ethyl-N1-pyrazinoyl-thiosemicarbazide 4 showed the highest activity against M. tuberculosis H37Rv (IC90 = 16.87 µg/ mL). Details of the structure-activity and structure-cytotoxicity relationships are discussed.

We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P'1 and P4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P4 position with hydrogen bond accepting groups and acidic moieties at the P'1 position with less acidic and similar molecular-size moieties (carboxylic acid or tetrazole bioisosteres). These inhibitors exhibited improved BACE1 inhibitory activities and a thorough quantitative structure–activity relationship study was performed.

A new long chain fatty alcohol acetate identified as 17-hydroxypentacosanyl acetate (1), together with a new xanthone identified as 1,8-dihydroxy-3,6-dimethoxy-xanthone-5-O-[-L-rhamnopyranosyl-(1"2')]--D-glycopyranoside (3), as well as two new lignans identified as (+)-lyoniresinol-3a-O-[-L-rhamnopyranosyl-(1"'6")]--D-glucopyranoside (4) and (+)-isolariciresinol-3a-O-[-L-rhamnopyranosyl-(1"'2")--L-rhamnopyranosyl-(1""6")--D-glucopyranoside (5), in addition to -sitosterol-3-O-acetate (2) were isolated from the methanolic extract of the aerial parts of Polygonum bellardii growing in Egypt. Their structures were elucidated on the basis of different chemical and spectroscopic evidences. The total extract and its fractions, in addition to compounds (3, 4 and 5) showed significant antioxidant potential by DPPH• scavenging activity technique.

A new long chain fatty alcohol acetate identified as 17-hydroxypentacosanyl acetate (1), together with a new xanthone identified as 1,8-dihydroxy-3,6-dimethoxy-xanthone-5-O-[-L-rhamnopyranosyl-(1"2')]--D-glycopyranoside (3), as well as two new lignans identified as (+)-lyoniresinol-3a-O-[-L-rhamnopyranosyl-(1"'6")]--D-glucopyranoside (4) and (+)-isolariciresinol-3a-O-[-L-rhamnopyranosyl-(1"'2")--L-rhamnopyranosyl-(1""6")--D-glucopyranoside (5), in addition to -sitosterol-3-O-acetate (2) were isolated from the methanolic extract of the aerial parts of Polygonum bellardii growing in Egypt. Their structures were elucidated on the basis of different chemical and spectroscopic evidences. The total extract and its fractions, in addition to compounds (3, 4 and 5) showed significant antioxidant potential by DPPH• scavenging activity technique.

The chloroformic fraction of the roots of Centaurium spicatum L. afforded one new xanthone named 1,5,8-trihydroxy-3,6,7-trimethoxyxanthone (1) together with six known xanthones (2–7), one of them isolated for the first time from a plant source (2). One secoiridoid glucoside (8) was also isolated. The structures of the isolated compounds were established based on 1D and 2D (1H–1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested for their antimicrobial and antiprotozoal activities. Compound 6 displayed moderate antifungal activity against Candida krusei and Cryptococcus neoformans with IC50 values of 12.8 and 17.9 g/ml respectively.

Two new acetylated flavonol glycosides, quercetin 3-O-[(2,4-diacetyl--L-rhamnopyranosyl)-(16)]-2,4-diacetyl--D-galactopyranoside (1) and quercetin 3-O-[(2,4-diacetyl--L-rhamnopyranosyl)-(16)]-3,4-diacetyl--D-galacto-pyranoside (2), in addition to two known acetylated quercetin glycosides quercetin 3-O-[(2,3,4-triacetyl--L-rhamnopyranosyl)-(16)--D-galactopyranoside (3) and quercetin 3-O-[(2,3,4-triacetyl--L-rhamnopyranosyl)-(16)-3-acetyl--D-galactopyranoside (4), were isolated from the aerial part of Centaurium spicatum (L.) Fritsch (Gentianaceae). Structure elucidation, especially the localization of the acetyl groups, and complete 1H- and 13C-NMR assignments of these biologically active compounds were carried out using one- and two-dimensional NMR measurements, including 1H- and 13C-NMR, DEPT-135, H–H COSY, HMQC and HMBC, in addition to HR-FAB/MS experiments.