Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization.

Background: Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis.

Design and total synthesis of (-)-codonopsinine, (-)-codonopsine and codonopsinine analogues by O-(2-oxopyrrolidin-5-yl)trichloroacetimidate as amidoalkylating agent with improved antimicrobial activity via solid lipid nanoparticle formulations.

A general strategy towards total synthesis of (-)-codonopsinine, (-)-codonopsine and codonopsinine analogues has been developed from (D)-tartaric acid via the intermediate (3S,4R)-1-methyl-2-oxo-5-(2,2,2-trichloroacetamido)pyrrolidinediacetate (7). α-amidoalkylation studies of 7 with electron rich benzene derivative 8a-g as C-nucleophiles afforded (aryl derivatives) 9a-g. The target compounds 1, 2 and 13c-g were readily obtained from 10a-gvia Grignard addition to the homochiral lactam which was produced by deoxygenation using Lewis-acid followed by deacetylation.

Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives.

The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines.

Design, Synthesis, and Molecular Docking of Novel Pyrrolooxazepinediol Derivatives with Anti-Influenza Neuraminidase Activity.

A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starting from l-tartaric acid, which was transformed into anhydride which then reacted with allylamine in xylene to afford the imide 2. The target molecules 12-15 were achieved via ring-closing metathesis with the Grubbs catalyst, followed by reduction of the carbonyl group and deprotection of hydroxyl groups. Finally, catalytic hydrogenation of the double bond afforded the title compounds 12-15.

Design, synthesis and pharmacological evaluation of omeprazole-like agents with anti-inflammatory activity.

A new series of novel benzimidazole derivatives containing substituted pyrid-2-yl moiety and polyhydroxy sugar conjugated to the N-benzimidazole moiety has been synthesized and evaluated as orally bioavailable anti-inflammatory agents with anti-ulcerogenic activity. The anti-inflammatory and anti-ulcerogenic activities of these compounds were compared to diclofenac and omeprazole, respectively. In carrageenan-induced paw oedema assay, 2-methyl-N-((3,4-dimethoxypyridin-2-yl)methyl)-1H-benzimidazol-5-amine (12d) and 1-(1,2,3,5-tetrahydroxy-α-D-mannofuranose)-5-(((3,4-dimethoxypyridin-2yl)methyl)amino)-2-methyl-1H-benzimidazole (15d) displayed dose-dependent anti-inflammatory activities by decreasing the inflammation by 62% and 72%, respectively which is comparable to that of diclofenac (73%).

Design, synthesis and antitumor activity of novel D-glucuronic acid derivatives.

A series of D-glucuronic acid derivatives were chemically synthesized including acetylated and deacetylated glucuronamides, as well as N-glucuronides starting from the D-glucuronic acid itself by means of protection/deprotection, activation and condensation protocols. Structure elucidation of all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in vitro antitumor activity against MCF-7, TK-10 and UACC-62 cell lines.

Synthesis of some novel D-glucuronic acid acetylated derivatives as potential anti-tumor agents.

A structurally diverse series of Δ(4,5) -uronamide derivatives have been chemically synthesized starting from D-glucuronic acid itself by means of acetylation, activation, amide bond formation and base-catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in-vitro anti-tumor activity against MCF-7, TK-10 and UACC-62 cell lines.

Novel benzimidazo[2,1-c][1,4]thiazinone derivatives with potent activity against HSV-1.

The synthesis of new 2-carboxymethylsulfanylmethyl-1H-benzimidazole and 1,3-dihydro-4H-benzo[4',5']imidazo[2,1-c][1,4]thiazine-4-one-8-carboxylic acid derivatives was investigated. The antiviral activity of compounds 1-14 was tested against the herpes simplex virus 1. Compounds 5 and 14 showed potent activity as they inhibited virus propagation by 94.

Structure-based design of benzimidazole sugar conjugates: synthesis, SAR and in vivo anti-inflammatory and analgesic activities.

A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranoside, 2,3,5,6-tetrahydroxy-alpha-D-mannofuranoside, 1:2,5:6-di-O-isopropylidene-alpha-D-gluco-furanose,3-O-benzyl-6,7-dideoxy-1:2-O-isopropylidene-alpha-D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7-dideoxy-1,2-dihydroxy-alpha-D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy-alpha-D-glucofuranose sugar moieties, were obtained in good yields from 2-methyl N-(trichloroacetamidomethyl)benzimidazole as a donor and carbohydrate residues as acceptor precursors in the presence of catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as Lewis acid. Compounds 6, 7, 10, 13, 15, and 16 showed significant anti-inflammatory and analgesic activities.