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New camphor hybrids: lipophilic enhancement improves antimicrobial efficacy against drug-resistant pathogenic microbes and intestinal worms

Using the Blanc reaction, new derivatives of camphor (1a?g) and camphor sulfonic acid (2a?g) were synthesized. Chemical structures of the new derivatives were supported by IR, 1H-NMR, 13C-NMR, and LC-MS/MS (ESI) spectrometric analyses. The new compounds (1a?g/2a?g) and the parent compounds (a?g) were tested for their antimicrobial efficacy against the following drug-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Klebsiella pneumonia (MDR-Kb), Escherichia coli (FDA control), Acinetobacter baumannii, Pseudomonas aeruginosa, Candida albicans (CLSI: Clinical and Laboratory Standards Institute strain) and Cryptococcus neoformans var. grubii. The linking of camphor to quinoxalin-2,3(1H, 4H)-dione (1a) enhances the antibacterial efficacy approximately 8-folds (MIC: 24 muM) against MRSA. Camphor linking with isatin (1g) increased efficacy against Acinetobacter baumannii by 8-fold (MIC: 26 muM) and by 4-fold (MIC: 51 muM) against MRSA, MDR-Kb, E. coli, P. auruginosa and C. albicans. Among the series, derivatives of benzoin (1e) and salicylic acid (1f) exhibited greater efficacy against drug-resistant Candida albicans, MDR-Kb and Acinetobacter baumannii, whereas 6, 7-biphenylquinoxalin 2-sulfonamide/sulphonyl chloride (1b/1d) selectively inhibited the growth of Gram-negative bacteria. None of these compounds were active against Cryptococcus neoformans var. grubii. Furthermore, these new derivatives were tested for anthelmintic efficacy and the results indicated that new compounds had significant anthelmintic efficacy (p < 0.05) at 2.5 mg/mL, except for the salicylic acid hybrids (1f, 2f). To conclude, camphor hybrids (1a?g) demonstrated enhanced antimicrobial and anthelmintic efficacy compared to the camphor sulfonic acid hybrids (2a?g). This improved antimicrobial efficacy may be due to the increased membrane permeability of the compounds across the cell wall, via the camphor moiety, which augmented the lipophilicity of the new compounds. A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 15804-19-0 Reference£º
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Benzopyrones. Part 23. Cyclization of o-Amino Carboxamides and Related Compounds

Cyclization of 2-amino-6-bromo-4-oxochromene-3-carboxamide (5) with diethyl oxalate-sodium ethoxide gave the benzopyrano<2,3-d>pyrimidine-4,6-dione (6).Ethyl 3-amino-2-carbamoyl-4-oxochromene-6-carboxylate (10a) in a similar reaction gave derivatives of a novel ring system benzopyrano<3,2-d>pyrimidine (8) but when 3-amino-4-oxochromene-2-carboxamide (10b) was subjected to the same reaction, the novel ring system benzopyrano<3,2-e>-1,4-diazepine (14a) was obtained in high yield.This structure, which contains the hitherto unknown 1,4-diazepine-2,3,5-trione ring, is supported by spectroscopic and chemical evidence.The presence of a 3-amino and a 2-carbonyl group in a chromone has an unexpected shielding effect on the chemical shift of C-8.The course of the cyclization was studied.Attempts to cyclize 3-aminomethyl-4-oxochromene-2-carboxamide (28; X= Y= H), a homologue of (10b), failed but a new ring system (31) was obtained when ethyl 3-bromo-4-oxochromene-2-carboxylate (29; R1= OEt) reacted with o-phenylenediamine.

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Mannich bases in medicinal chemistry and drug design

The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors.

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Synthesis, Characterization and Antimicrobial Activity of 1,2-dihydroquinoxaline-3-yl-3-Substitutedphenyl-1H-pyrazole-4-Carbaldehyde

A series of 1,2-dihydroquinoxaline-3-yl-3-substitutedphenyl-1H-pyrazole-4-carbaldehyde were synthesized and evaluated for their antimicrobial activity against two Gram-positive and two Gram-negative organisms and two fungal organisms. The study has shown that pyrazole-4-carbaldehyde-incorporated quinoxaline was essential for activity. Among the compounds, 5a, 5c, 5d had shown significant activity against all selected strains when compared with control. These compounds may prove useful as antimicrobial agents.

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Synthesis of benzimidazole-2-carboxylic acid amides from o-phenylenediamine and oxamic acid esters

A method for the preparation of N-R amides of benzimidazole-2-carboxylic acid on the basis of the reaction between o-phenylenediamine and esters of N-R oxamic acids was developed.

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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Compounds of Formulas I-VI, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth. Formula I is exemplified below: Formula (i)

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Theoretical and experimental investigation of acidity of the glutamate receptor antagonist 6,7-dinitro-1,4-dihydroquinoxaline-2,3-dione and Its Possible Implication in GluA2 Binding

The acidity of organic compounds is highly relevant to understanding several biological processes. Although the relevance and challenges in estimating pKa values of organic acids is recognized by several reported works in the literature, there is a lack in determining the acidity of amides. This paper presents an experimental/theoretical combined investigation on the acid dissociation of the compound 6,7-dinitro-1,4-dihydroquinoxaline-2,3-dione (DNQX), a well-established antagonist of ionotropic glutamate receptor GluA2. DNQX was synthesized, and its two acidic constants were determined by UV-vis spectroscopy. The experimental pKa of 6.99 ¡À 0.02 and 10.57 ¡À 0.01 indicate that DNQX mainly exists as an anionic form (DNQXA1) in physiological media, which was also confirmed by 1H NMR analysis. Five computational methods were applied for estimating the theoretical pKa values of DNQX, including B3LYP, M06-2X, omegaB97XD, and CBS-QB3, which were able to provide reasonable estimates for pKa associated with DNQX. Molecular dynamics studies have demonstrated that DNQXA1? binds more effectively to the pocket of the GluA2 than neutral DNQX, and this fact is coherent to the interactions between amidic oxygens and Arg845 being the main interactions of this host-guest system. Moreover, interaction of GluA2 with endogenous glutamate is stronger than that with DNQXA1, which is in agreement with literature. To the best of our knowledge, we report herein an unprecedented approach involving acidity of the antagonist DNQX, as well as the possible implications in binding to GluA2.

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A solvent-free one step conversion of ketones to amides via Beckmann rearrangement catalysed by FeCl3¡¤6H2O in presence of hydroxylamine hydrochloride

FeCl3¡¤6H2O catalyses the direct conversion of ketones to amides via Beckmann rearrangement in the presence of hydroxylamine hydrochloride in good to excellent yields. No additional organic solvent is required. This solid phase reaction involves in situ formation of oxime, cleavage of C-C bond and formation of C-N bond. FeCl3¡¤6H2O is inexpensive, stable, easy to handle and eco-friendly.

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Solvent-free reaction using phosphonium salts: Chlorination of hydroxyheteroaromatics and dehydration of primary amides

Solvent-free chlorination of heteroaromatics using the phosphonium salt, prepared by reaction of triphenylphosphine with N-chlorosuccinimide, was accomplished by microwave-irradiation or heating to give the corresponding chloroheteroaromatics. Similarly, primary amides was converted into nitriles by this method.{A figure is presented}.

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Pyrrolo[2,3-b]quinoxalines as inhibitors of firefly luciferase: Their Cu-mediated synthesis and evaluation as false positives in a reporter gene assay

2-Substituted pyrrolo[2,3-b]quinoxalines having free NH were prepared directly from 3-alkynyl-2-chloroquinoxalines in a single pot by using readily available and inexpensive methane sulfonamide (or p-toluene sulfonamide) as an ammonia surrogate. The reaction proceeded in the presence of Cu(OAc)2 affording the desired product in moderate yield. The crystal structure analysis of a representative compound and its supramolecular interactions are presented. Some of the compounds synthesized exhibited inhibitory activities against luciferase that was supported by the predictive binding mode of these compounds with luciferase enzyme through molecular docking studies. The key observations disclosed here can alert users of luciferase reporter gene assays for possible false positive results due to the direct inhibition of luciferase.

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