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Plasmodium falciparum PFI1625c offers an opportunity to design potent anti-malarials: Biochemical characterization and testing potentials in drug discovery.

Putative PFI1625c was cloned, over-expressed and purified to homogeneity. It is a 56.2 kDa monomeric protease which preferentially catalyzes the degradation of gelatin with a Km = 30μM. It is a slow acting enzyme with optimal pH 8.5 and temperature 37 °C, and activity is sensitive to metalloprotease inhibitor 1,10-phenanthroline. PFI1625c active site was probed with a series of heterocyclic compounds and three molecules namely, BNPC-Inh2, DDBM-Inh1 and BHPM-Inh1 from the series were inhibiting PFI1625c protease activity. These heterocyclic compounds were found to irreversible inhibiting PFI162…

Design, synthesis and activity evaluation of novel quinazolinone compounds as TRPC5 inhibitors.

The TRPC5 channel plays an important role in regulating various physiological processes, which is related to various human diseases, especially psychiatric and kidney diseases. Although the TRPC5 channel is one of the essential potential target, no drugs against TRPC5 channels have been granted in the market to date. In this study, based on the structure of hit compound ph1, we further synthesied 49 compounds of novel quinazolinone and heterocyclic fusion pyrimidinone derivatives, and their activities were evaluated by electrophysiological assays. After extensive screening, 21 compounds exhibi

Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IV with heterocyclic mercaptans, sulfenamides, sulfonamides and their metal complexes.

A series of sulfenamides, sulfonamides and sulfonamide metal complexes have been prepared starting from 4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives. The heterocyclic mercaptans were oxidized to the corresponding sulfenamides by hypochlorite in the presence of ammonia. The sulfonamides were obtained by oxidation of sulfenamides with potassium permanganate. The Zn(II) and Cu(II) complexes of the new heterocyclic sulfonamides have been prepared via the sodium salt of the ligand. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human, b = bovine) with

Heterocyclic ring expansion yields anthraquinone derivatives potent against multidrug resistant tumor cells.

Chemical modifications of anthraquiones are aimed at novel derivatives with improved antitumor properties. Emergence of multidrug resistance (MDR) due to overexpression of transmembrane ATP binding cassette transporters, in particular, MDR1/P-glycoprotein (Pgp), can limit the use of anthraquinone based drugs. Previously we have demonstrated that annelation of modified five-membered heterocyclic rings with the anthraquinone core yielded a series of compounds with optimized antitumor properties. In the present study we synthesized a series of anthraquinone derivatives with six-membered heterocyc

Assessing the Multitarget Therapeutic Potential of Novel 9-Aminoacridine Derivatives for Alzheimer's Disease.

The escalating number of Alzheimer's disease (AD) cases and the limitations of current therapies pose a significant threat to human health, necessitating the discovery of novel drugs with innovative modes of action. To address this challenge, we pursued multitarget ligand strategy with the expectation of improved disease management. Continuing our efforts to discover new multitarget agents for AD, we decorated the planar 6-Cl-2-OCH3-9-aminoacridine core with basic heterocyclic or benzyl side chains as polar and hydrophobic structural features, respectively. All the compounds inhibited acetylch

Alkali metal N-heteroarenes as a new family of luminescent materials.

Organic-based luminescent materials have broad applications across illumination, display, and imaging. However, intramolecular vibrations and intermolecular interactions, such as π-π stacking, can induce non-radiative transition and lead to low efficiency and fluorescence quenching for solid-state materials, especially for small conjugated molecules. In the present study, a facile yet versatile conceptual approach to fabricate a new type of luminescent materials, i.e., alkali metal N-heteroarene salts, was developed via a metal substitution strategy. Over 30 solid-state ionic compounds have be

Discovery and semisynthesis of coniochaetones N-P: antimicrobial and antioxidant heterocyclics from an Antarctic-derived fungus Penicillium sp. S2014503.

Penicillium sp. S2014503 is a fungus found in the Antarctic. Herein, we report a new heterocyclic (1) and two semi-synthesized ones (2-3) derived from citrinin (4), the main product of S2014503. Absolute configurations of 1 and 4 were deduced by single crystal X-ray diffraction analyses. Compound 2 was analyzed to be a diastereomeric mixture. The structure of compound 3 was determined by NMR and X-ray diffraction analyses. Compounds 2 and 3 showed strong antibacterial activity. Furthermore, compounds 1-4 exhibited excellent synergistic effects against Candida albicans SC5314 by inhibiting its

Photocatalytic Dual Carbon-Carbon Bond Cleavage Cross-Coupling Reaction between Vicinal Dicarbonyl Compounds and Carboxylic Acids.

Carbon-carbon bond cleavage reactions enable the efficient recombination of two organic molecules to generate new complex organic compounds. This study developed a novel photocatalytic dual carbon-carbon bond cleavage cross-coupling reaction between vicinal dicarbonyl compounds and carboxylic acids. The reaction proceeds under mild conditions and can be used for the synthesis of target products containing sensitive chemical bonds and various heterocyclic skeletons. Through a series of control experiments, including fluorescence quenching experiments, light on/off experiments, and free radical

Recent advances in piperazine derivatives as antibacterial agents: a comprehensive review (2020-2024).

Antimicrobial resistance (AMR) is a major global health challenge that requires the development of new therapeutic drugs. Piperazine, a privileged nitrogen-containing heterocyclic scaffold, has been identified as a viable framework for antibacterial drug development. This review examines current breakthroughs (2020-2024) in piperazine-based compounds with antibacterial activity. We discuss their structural modifications and potency against multidrug-resistant bacterial strains. Special importance is placed on newly synthesized compounds demonstrating high efficacy, as well as their structure-a

Indazole and its Derivatives in Cardiovascular Diseases: Overview, Current Scenario, and Future Perspectives.

Indazoles are a class of heterocyclic compounds with a bicyclic ring structure composed of a pyrazole ring and a benzene ring. Indazole-containing compounds with various functional groups have important pharmacological activities and can be used as structural motifs in designing novel drug molecules. Some of the indazole-containing molecules are approved by FDA and are already in the market. However, very few drugs with indazole rings have been developed against cardiovascular diseases. This review aims to summarize the structural and pharmacological functions of indazole derivatives which hav…

Characterization of volatile organic compounds with anti-atherosclerosis effects in Allium macrostemon Bge. and Allium chinense G. Don by head space solid phase microextraction coupled with gas chromatography tandem mass spectrometry.

INTRODUCTION: Allium macrostemon Bge. (AMB) and Allium chinense G. Don (ACGD) are both edible Allium vegetables and named officinal Xiebai ( … ACGD, respectively. Relative-quantification results also confirmed sulfur compounds, aldehydes, and heterocyclic compounds accounted for about 85.6% in AMB bulbs, while approximately 86.6% in ACGD bulbs were attributed to sulfur compounds, ketones, and heterocyclic compounds. Multivariate statistical analysis showed 62 differentially expressed VOCs were observed between …

Theoretical Photoelectron Spectroscopy of Low-Valent Carbon Species: A ∼6 eV Range of Ionization Potentials among Carbenes, Ylides, and Carbodiphosphoranes.

High-quality density functional theory calculations underscore a nearly 6 eV range for the ionization potentials (IPs) of neutral, low-valent carbon compounds, including carbenes, ylides, and zero-valent carbon compounds (carbones) such as carbodiphosphoranes (CDPs) and carbodicarbenes. Thus, adiabatic IPs as low as 5.5 ± 0.1 eV are predicted for CDPs, which are about 0.7-1.2 eV lower than those of simple phosphorus and sulfur ylides. In contrast, the corresponding values for N-heterocyclic carbenes are about 8.0 eV while those for simple singlet carbenes such as dichlorocarbene and difluoroca

Synthesis, Characterization and Antimicrobial Evaluation of Novel 6'- Amino-spiro[indeno[1,2-b]quinoxaline[1,3]dithiine]-5'-carbonitrile Derivatives.

l,3-Dithiin with two sulfurs in its structure is a six-membered, sulfur-containing heterocyclic compound. New derivatives of 6'-amino-2'-(arylidene)spiro[indeno[1,2-b]quinoxaline[1,3]dithiine]-5'-carbonitrile were prepared by the multi-component reaction of active methylene compounds, carbon disulfide, malononitrile and multi-ring compounds containing a carbonyl group in the presence of piperidine as a catalyst at room temperature with high efficiency. The antimicrobial effects including antibacterial and antifungal effects based on inhibition zone diameter (IZD), minimum inhibitory concentrat

DNA binding compounds targeting fungal pathogens: an emerging concept in the discovery of novel antifungal agents.

With the urgent need for novel agents to combat emerging fungal resistance to existing drugs, activity in the exploration of small molecule DNA binders has increased. Recently, selected cationic heterocyclic compounds belonging to a broad class of molecules known to bind to the minor groove of DNA were revealed to have potent antifungal activity. These molecules are different from the conventional DNA-interacting drugs such as topoisomerase inhibitors, DNA alkylators or intercalators. Selected compounds are fungicidal towards a variety of pathogenic yeasts and molds, and a selected lead compou…

Sulfenamido-sulfonamides as inhibitors of carbonic anhydrase isozymes I, II and IV.

Reaction of 2-nitrophenyl- and 4-nitrophenylsulfenyl-chlorides with aromatic/heterocyclic sulfonamides containing a free amino group afforded sulfenamido-sulfonamides, which were inhibitors of the zinc enzyme carbonic anhydrase (CA). Oxidation of these derivatives with potassium permanganate in acetone led to the corresponding bis-sulfonamides. Good inhibition of three CA isozymes (CA I, II and IV, respectively) was observed with some of the new compounds, the bis-sulfonamides being more active than the sulfenamido-sulfonamides. A possible in vivo transformation of the last type of compounds,

Electrochemical Difunctionalization of Terminal Alkynes: Access to 1,4-Dicarbonyl Compounds.

1,4-Dicarbonyl compounds are versatile scaffolds for the heterocycle synthesis, including the Paal-Knorr reaction. Herein, a feasible electrosynthesis method to access 1,4-dicarbonyl compounds has been developed from simple alkynes and 1,3-dicarbonyl compounds. When the undivided cell is combined with the constant current mode, aryl alkynes containing numerous medicinal motifs with 1,3-dicarbonyl esters or ketones react smoothly. External oxidant and catalyst-free conditions conform to the requirements of green synthesis.

Enantioselective Access to Trifluoromethylated Spirocyclopropyl Heterocycles.

Chiral spirocyclopropyl heterocycles have emerged as privileged three-dimensional structural motifs in medicinal chemistry. Nevertheless, efficient catalytic enantioselective assembly of such compounds still faces considerable synthetic difficulties. Herein, we describe a rhodium-mediated asymmetric [2+1] cyclopropanation reaction using methylene azacycles and fluoroalkyl triftosylhydrazones as reaction partners, which offers a concise synthetic route toward enantioenriched trifluoromethylated spirocyclopropyl heterocyclic derivatives. This synthetic transformation tolerates various substrates

Экспериментирование гетероциклов (2013-22 годы) в качестве потентных фармакофоров при разработке лекарственных препаратов для мультиклероза.

Множественный склероз (MS) — демиелинизирующая болезнь, в которой поврежден изоляционный покров (милиновая оболочка) мозга и спинного мозга. Разрушение приводит к снижению передачи сигнала в нервной системе. Симптомы включают двойное зрение, слабость мышц и трудности с координацией. Предполагалось, что генетические и вирусные инфекции являются правдоподобными факторами, влияющими на НР. Несмотря на то, что у них нет лекарств, лечение предотвращает будущие нападения. В настоящее время химиотерапия и моноклонные антитела являются доступными средствами для лечения MS. В настоящее время гетероцикл

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a demyelinating disease in which the insulating cover (myelin sheath) of the brain and spinal cord is damaged. De … re attacks. At present, chemotherapy and monoclonal antibodies are the available treatments for MS. Heterocyclic compounds are currently being tested clinically for their efficacy. Some heterocyclic scaffolds have been found to be promising for the treatment of MS. In view of this, research has been conducted towards the design and discovery of chemical agents for MS. H …

Vinylphosphonium and 2-aminovinylphosphonium salts - preparation and applications in organic synthesis.

The main synthetic routes towards vinylphosphonium salts and their wide applications in organic synthesis are discussed in this review. Particular attention is paid to the use of these compounds as building blocks for the synthesis of carbo- and heterocyclic systems after their prior transformation into the corresponding phosphorus ylides, followed by the intramolecular Wittig reaction with various types of nucleophiles containing a carbonyl function in their structures.

Copper-catalyzed cascade synthesis of alkyl 6-aminobenzimidazo[2,1-a]isoquinoline-5-carboxylates.

A convenient and efficient copper-catalyzed cascade method has been developed for synthesis of benzimidazoisoquinoline derivatives via reactions of readily available substituted 2-(2-halophenyl)benzoimidazoles with alkyl cyanoacetates under mild condition, and the corresponding alkyl 6-aminobenzimidazo[2,1-a]isoquinoline-5-carboxylates were obtained in good to excellent yields. The novel method provides diverse and useful poly N-heterocyclic compounds for combinatorial chemistry and medicinal chemistry.