An Investigation on Linker Modifications of Cyanoguanidine-Based P2X7 Receptor Antagonists.

Despite their acknowledged significance in the inflammatory signalling cascade across a range of disease states, P2X7R antagonists have not yet proven to be effective in clinical trials. In this study, we present findings on P2X7 receptor antagonists that are based on a core adamantyl-cyanoguanidine-quinoline lead. To investigate the specific features of the cyanoguanidine moiety that influence compound potency we carried out a structure-activity relationship (SAR) study.

Water-Soluble Arylazoisoxazole Photoswitches.

Azoheteroarenes are emerging as powerful alternatives to azobenzene molecular photoswitches. In this study, water-soluble arylazoisoxazole photoswitches are introduced. UV/vis and NMR spectroscopy revealed moderate to very good photostationary states and reversible photoisomerization between the E- and Z-isomers over multiple cycles with minimal photobleaching.

Highly productive and scalable approach to synthesize ticlopidine: A potent thienopyridine anti-platelet aggregation drug.

Ticlopidine (trade name Ticlid), an acidic thienopyridine derivative, is an effective, well-known and long-acting inhibitor of platelet aggregation. Because of its potent inhibitory activity for treating a variety of diseases, the development of efficient approaches for accessing ticlopidine represents an important endeavour. Therefore, in this research work, we developed a promising novel five-step synthetic approach for synthesizing ticlopidine.

Ultra-Low Molecular Weight Photoswitchable Hydrogelators.

Two photoswitchable arylazopyrozoles form hydrogels at a concentration of 1.2 % (w/v). With a molecular weight of 258.

Anion Binding Affinity: Acidity versus Conformational Effects.

High-level quantum chemical calculations were used to elucidate the gas- and solution-phase conformational equilibria for a series of symmetrically substituted (thio)ureas, (thio)squaramides, and croconamides. Gas-phase calculations predict that the thermodynamic conformer of many of these anion receptors is not the dual-hydrogen-bond-facilitating anti-anti conformer as is commonly assumed. For ,'-diaryl thiosquaramides and croconamides, the syn-syn conformer is typically the predominant conformer.

New aryl Schiff bases of thiadiazole derivative of ibuprofen as DNA binders and potential anticancer drug candidates.

The work presented in this paper describes the synthesis of two new aryl Schiff bases [()--(4-(benzyloxy)-3-methoxybenzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-1) and [()--(4-(benzyloxy)benzylidene)-5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine] (ASB-2). These compounds were characterized by different analytical techniques and then studied for DNA binding. Binding studies were carried out at neutral pH (7.

Synthesis, antibacterial activity and molecular docking study of vanillin derived 1,4-disubstituted 1,2,3-triazoles as inhibitors of bacterial DNA synthesis.

Antimicrobial resistance (AMR) compelled scientists in general while pharmacists, chemists and biologists in specific to believe that we could always remain ahead of the pathogens. The pipeline of new drugs is running gasping and the inducements to develop new antimicrobials to address the global problems of drug resistance are weak. In this pursuit, effective endeavours to prepare new anti-bacterial entities is highly wished.

Design, synthesis and biological evaluation of trinary benzocoumarin-thiazoles-azomethines derivatives as effective and selective inhibitors of alkaline phosphatase.

Design, synthesis and characterization of new trinary Benzocoumarin-Thiazoles-Azomethine derivatives having three bioactive scaffolds in a single structural unit were carried out. The newly synthesized molecules were investigated for the inhibitory activity on human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP) isozymes. All the tested compounds exhibited the potent inhibition profile on both isozymes of alkaline phosphatase i.

Synthesis, molecular docking and kinetic studies of novel quinolinyl based acyl thioureas as mushroom tyrosinase inhibitors and free radical scavengers.

The enzyme tyrosinase plays a vital role in melanin biosynthesis and enzymatic browning of vegetables and fruits. A series of novel quinolinyl thiourea analogues (11a-j) were synthesized by reaction of 3-aminoquinoline and corresponding isothiocyanates, in moderate to excellent yields with different substitutions and their inhibitory effect on mushroom tyrosinase and free radical scavenging activity were evaluated. The compound N-(quinolin-3-ylcarbamothioyl)hexanamide (11c) exhibited the maximum tyrosinase inhibitory effect (IC = 0.

Recent developments and comparison of transformation strategies for organic halides to aldehydes and ketones.

Aldehydes and ketones are parts of millions of compounds and are important classes of chemicals which serve as important precursors for the synthesis of library of compounds. For the synthesis of aldehydes and ketones, one impressive approach to date, because of its excellent selectivity, high yield and stability toward over-reduction and over-oxidation, is the oxidation of organic halides (viz. aliphatic and benzyl halides).

Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics.

A series of symmetrical salicylaldehyde-bishydrazine azo molecules, -, have been synthesized, characterized by H-NMR and C-NMR, and evaluated for their in vitro α-glucosidase and α-amylase inhibitory activities. All the synthesized compounds efficiently inhibited both enzymes. Compound was the most potent derivative in the series, and powerfully inhibited both α-glucosidase and α-amylase.

Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT, and DNA-Binding Studies of (E)-2-(3-Hydroxy-4-Methoxybenzylidene)Hydrazinecarbothioamide.

(E)-2-(3-Hydroxy-4-methoxybenzylidene)hydrazinecarbothioamide 3 was synthesized by reacting thiosemicarbazide with 2-hydorxy-3-methoxybenzaldehyde in dry ethanol. The structure was elucidated by spectroscopic (FT-IR, H NMR, and C NMR) and single crystal X-ray diffraction techniques. A detailed analysis of the intermolecular interactions has been performed based on the Hirshfeld surfaces and their associated two-dimensional fingerprint plots.

Synthesis of novel ()-1-(2-(2-(4(dimethylamino) benzylidene) hydrazinyl)-4-methylthiazol-5-yl)ethanone derivatives as ecto-5'-nucleotidase inhibitors.

Ecto-5'-nucleotidase (e5'NT), a membrane-bound enzyme and an essential member of ecto-nucleotidases which regulates extracellular purinergic signalling. Their upregulation results in various disease conditions, for example, inflammation, hypoxia and cancer. Therefore, efforts have been made to synthesize potent and selective inhibitors of e5'NT.

Drug-1,3,4-Thiadiazole Conjugates as Novel Mixed-Type Inhibitors of Acetylcholinesterase: Synthesis, Molecular Docking, Pharmacokinetics, and ADMET Evaluation.

A small library of new drug-1,3,4-thiazidazole hybrid compounds (⁻) was synthesized, characterized, and assessed for their acetyl cholinesterase enzyme (AChE) inhibitory and free radical scavenging activities. The newly synthesized derivatives showed promising activities against AChE, especially compound (IC 18.1 ± 0.

Synthesis of sulfonamide, amide and amine hybrid pharmacophore, an entry of new class of carbonic anhydrase II inhibitors and evaluation of chemo-informatics and binding analysis.

Selective inhibition of carbonic anhydrase (CA) enzyme is an active area of research for medicinal chemists. In the current account, a hybrid pharmacophore approach was employed to design sulfonamide, amide and amine containing new series of potent carbonic anhydrase II inhibitors. The aromatic fragment associated with pharmacophore was altered suitably in order to find effective inhibitors of CA-II.

Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies.

The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis.

One-pot four-component synthesis of thiazolidin-2-imines using Cu/Zn dual catalysis: A new class of acetylcholinesterase inhibitors.

An efficient one-pot four-component strategy involving aldehydes, amines, alkynes and isothiocyanates has been developed to access a novel series of thiazolidine-2-imines (5a-x). This process operates under the action of a cooperative catalysis composed of Cu(I) and Zn(II) delivering the desired five-membered heterocyclic compounds in good to excellent yields. Notably, this transformation avoids the use of pre-formed imines or propargylamines and proceeds via an intramolecular 5-exo-dig hydrothiolation reaction of the in situ formed propargyl thiourea.

1-(2-Hydroxy-5-((trimethylsilyl)ethynyl)phenyl)ethanone based α,β-unsaturated derivatives an alternate to non-sulfonamide carbonic anhydrase II inhibitors, synthesis via Sonogashira coupling, binding analysis, Lipinsk's rule validation.

A novel series of silyl-yne containing chalcone derivatives 5a-5j was synthesized by exploiting Sonogashira coupling reaction and Claisen-Schimdt condensation reaction. The synthesized derivative were characterized by spectroscopic and elemental analysis. The selective inhibition of carbonic anhydrases is considered critical in the field of medicinal chemistry because carbonic anhydrases exits in several isoforms.

Synthesis, molecular docking and comparative efficacy of various alkyl/aryl thioureas as antibacterial, antifungal and α-amylase inhibitors.

Thioureas are exquisite building blocks for the construction of five and six membered heterocyclic units, and also display an extensive range of biological activities. 4-Nitro-2-cyano aniline was reacted with the various acid chlorides which were freshly prepared from carboxylic acids to afford the desired products in good yield. All the newly synthesized compounds were evaluated antibacterial, antifungal, antioxidant and α-amylase activity.

Synthesis, theoretical, spectroscopic and electrochemical DNA binding investigations of 1, 3, 4-thiadiazole derivatives of ibuprofen and ciprofloxacin: Cancer cell line studies.

Two new 1,3,4-thiadiazole derivatives of ibuprofen and ciprofloxacin namely {(5-(1-(4-isobutylphenyl)ethyl)-1,3,4-thiadiazol-2-amine)} 1 and {(3-(5-amino-1,3,4-thiadiazol-2-yl)-1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one)} 2 were synthesized and characterized by spectroscopic and elemental analysis. DFT and molecular docking were done initially for theoretical binding possibilities of the investigated compounds. In vitro DNA binding investigations were carried out with UV-visible spectroscopic, fluorescence spectroscopic, cyclic voltammetric (CV) experiments under physiological conditions of the stomach (4.

Exploration of carboxy pyrazole derivatives: Synthesis, alkaline phosphatase, nucleotide pyrophosphatase/phosphodiesterase and nucleoside triphosphate diphosphohydrolase inhibition studies with potential anticancer profile.

In the present work we report the synthesis of new aryl pyrazole derivatives using 1,3-dicarbonyl motifs. The reaction was proceeded by the cyclization of pentane-2,4-dione (1a), 3-chloropentane-2,4-dione (1b) or ethyl 3-oxobutanoate (1c) with different aryl hydrazines. The products, which can be regarded as 1H-pyrazol-1-yl-one analogues (3a-f, 3g-o, 4a-c, 5a-b) and represent drug like molecules along with well-developed structure-activity relationships, were obtained in good to excellent yield.

Novel 1,3-oxazine-tetrazole hybrids as mushroom tyrosinase inhibitors and free radical scavengers: Synthesis, kinetic mechanism, and molecular docking studies.

A variety of 5-(2H-tetrazol-5-yl)-4-thioxo-2-(substituted phenyl)-4,5-dihydro-1,3-oxazin-6-ones (3a-k) have been synthesized from 1,3-oxazine-5-carbonitriles (2a-k). The protocol represents an efficient, facile, and novel route from easily available precursors to unprecedented structures that share 1,3-oxazine and tetrazole motifs of utmost value. All the synthesized compounds (3a-k) were evaluated for their inhibitory potential against mushroom tyrosinase.

Synthesis of sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, pharmacokinetic properties, lead optimization, Lineweaver-Burk plot evaluation and binding analysis.

To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series (4a-4j) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis.

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid.

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico.