Solvent‐free Synthesis of Water‐Soluble New Pyridinium Amines: Spectroscopic Characterization,Biological Screening,and Interaction Study with DNA

New water‐soluble pyridinium amines ( 2–8 ) were obtained by the solid‐state reactions of 4‐chloro‐1‐methylpyridin‐1‐ium triflate ( 1 ) and various primary aromatic amines. These compounds were characterized by ¹H , ¹³C NMR , FTIR , UV –vis, and fluorescence spectroscopic methods along with single‐crystal X‐ray structure determination. The interaction potentials of all newly synthesized compounds with calf thymus DNA (CT‐DNA ) were investigated by UV –vis and florescence spectroscopy accompanied by docking studies. UV –vis spectroscopy indicated that the binding of compounds with CT‐DNA takes place via the intercalative mode. The compounds were also screened for their potential as antioxidants and enzyme inhibition agents. Some compounds displayed excellent butyrylcholine and acetylcholine esterase inhibition activities and were effective in scavenging the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH ) radical in a dose‐dependent manner comparable to a standard.     

Design and Synthesis of Photoaffinity Probe Candidates for the GABA-gated Chloride Channel

In order to characterize binding sites of insecticidal compounds on GABA gated chloride channel,new photoaf-finity probe candidates based on 5e-t-butyl-2e-[4-(substituted-propynyl)phenyl]-1,3-dithiane for the noncompetitiveblocker(NCB)site of the γ-aminobutyric acid(GABA)-gated chloride channel were designed and synthesized,andtheir potency as an inhibitor on NCB was measured by 4'-ethynyl-4-n-[2,3-~3H_2]-propylbicycloorthobenzoate(~3HEBOB)assay.The synthesized compounds showed high inhibition activities with half maximum inhibition concen-trations(IC_(50))of lower than 35 nmol/L and were very stable in binding conditions as well photoreacted quickly at300 nm light.These new compounds are expected to be good photoaffinity labeling probes if radioisotope iodine isincorporated.     

Synthesis,Voltammetric and Analytical Applications of Some Fluorine Substituted Spirosteroidalthiazolidin‐4‐one Derivatives of Sulfa Drugs

A new 5‐arylidene‐4‐oxo‐(sulfonamoyl phenyl)‐spiro[thiazolidinone‐2,2′‐steroids] series (7–10) was prepared by condensation of sulfanilamide, sulfapyridine and sulfadiazine sulfa drugs with testosterone, epiandrosterone and progesterone steroids, respectively. The resultant imino derivatives 1–3 upon cycloaddition with thioacetic acid in dry 1,4‐dioxane afforded 3‐sulfo‐namoylphenylspiro[4‐oxo‐thiazolidin‐2,2′steroids] (4–6). The latter compounds (4–6) upon condensation with p‐fluorobenzaldehyde in ethanol‐piperidine yielded the corresponding 4‐fluoroarylidene derivatives 7, 8 & 9, respectively. All the newly synthesized compounds were confirmed by UV, IR, ¹H NMR, ¹³C NMR, mass spectral data, elemental analysis and molecular weight determination. In vitro antimicrobial screening of some of the synthesized compounds showed good antimicrobial activities towards some pathogenic Gram‐positive, Gram‐negative bacteria and fungi vs. piperacillin and mycostatine antibiotics as standard antibacterial and antifungal agents, respectively. The voltammetric behavior of two newly spirothiazolidinone steroids ( 2a & 5a ) was critically studied. Compound 5a physically immobilized polyurethane foam solid sorbent was successfully used for removal and/or separation of bismuth(III) from water.     

Synthesis,antimicrobial, and antioxidant activities of new pyridyl‐ and thiazolyl‐bearing carbohydrazides

A series of novel substituted (E)‐N′‐benzylidene‐4‐methyl‐2‐(2‐propylpyridin‐4‐yl)thiazole‐5‐carbohydrazide derivatives ( 6a‐l ) have been synthesized by following the multistep synthetic route starting from prothionamide. The resulting compounds were characterized via ¹H, ¹³C NMR, and HRMS spectral data. The synthesized carbohydrazides were evaluated for their in vitro antimicrobial and antioxidant activities. Tested molecules have displayed moderate to good growth inhibition activity. Among the screened compounds, 6b , 6e , 6j, and 6k are found to be the more promising antimicrobial agents. A 2,2‐diphenyl‐1‐picrylhydrazyl assay was used to test the antioxidant activity of the carbohydrazides. The carbohydrazide derivatives 6b and 6i have shown better free‐radical scavenging ability than the other investigated compounds.     

Aloeverasides A and B: Two Bioactive C‐Glucosyl Chromones from Aloe vera Resin

Two new C‐glucosyl chromones named aloeverasides A ( 1 ) and B ( 2 ) were isolated from the resin of Aloe vera (L.) Burm.f . The structures of the two new natural products were elucidated based on 1D‐ (¹H‐ and ¹³C‐NMR) and 2D‐NMR (COSY, HSQC, and HMBC) spectroscopic techniques and mass spectrometry (ESI‐MS). Aloeverasides A ( 1 ) and B ( 2 ) were evaluated for their anticancer activity, and both induced a 76.4 and 70.5% growth inhibition of the breast cancer cell line (MDA‐MB‐231) at a concentration of 100 μm . Both compounds were also evaluated for their 1,1‐diphenyl‐2‐picryl‐hydrazyl antioxidant, urease enzyme, and α‐glucosidase enzyme inhibition activities. Aloeverasides A ( 1 ) and B ( 2 ) displayed good urease enzyme inhibition activities (62 and 55%, resp.), as well as antioxidant activity in which aloeveraside A ( 1 ) had a value of 60% inhibition, while aloeveraside B ( 2 ) demonstrated a more potent antioxidant activity with 80% inhibition.     

Design and Synthesis of Novel EGFR Inhibitors with L‐Rhamnose–Benzoxazinone Hybrids

Four L ‐rhamnose–benzoxazinone compounds as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were designed and synthesized. All structures of the compounds were characterized by ¹H‐NMR, ¹³C‐NMR, and high‐resolution mass spectrometry. The inhibition activities of the target compounds for the EGFR tyrosine kinase activity in vitro were determined. Compounds 6a , 6b , 6c , 6d displayed moderate activity in targeting EGFR.     

Design,Synthesis, and In Vitro Antileishmanial and Antitumor Activities of New Tetrahydroquinolines

A novel series of tetrahydroquinolines containing acetohydrazide, oxopyrazole, oxothioxodihydropyrazole, and thioxotriazole have been synthesized. Antileishmanial, antitumor, and cytotoxicity activities of synthesized compounds were evaluated in vitro. Antileishmanial activity of the most synthesized compounds showed tremendous activity towards Leishmania major. Most of the test compounds exhibited significant level of tumor inhibition. The tetrahydropyrano[2,3‐b]quinolin‐2‐one 6 and 4‐oxo‐4H‐pyrazol‐3‐yloxytetrahydroquinoline‐3‐carbonitrile derivatives 18 showed 100% tumor inhibition comparable with standard drug vincristine (100% tumor inhibition). Tetrahydroquinolines under investigation showed cytotoxicity with LD₅₀ values in the range 0.56–3.01 μg/mL compared with standard drug MS‐222 with LD₅₀ value of 4.30 μg/mL. The presence of a pyrazole ring markedly improved the activity profiles of tetrahydroquinoline. All newly synthesized compounds were characterized by IR, ¹H NMR, and MS.     

Synthesis and catalytic application of Pd complex catalysts: Atom‐efficient cross‐coupling of triarylbismuthines with haloarenes and acid chlorides under mild conditions

Palladium‐catalysed cross‐coupling reactions are some of the most frequently used synthetic tools for the construction of new carbon–carbon bonds in organic synthesis. In the work presented, Pd(II) complex catalysts were synthesized from palladium chloride and nitrogen donor ligands as the precursors. Infrared and ¹H NMR spectroscopic analyses showed that the palladium complexes were formed in the bidentate mode to the palladium centre. The resultant Pd(II) complexes were tested as catalysts for the coupling of organobismuth(III) compounds with aryl and acid halides leading to excellent yields with high turnover frequency values. The catalysts were stable under the reaction conditions and no degradation was noticed even at 150°C for one of the catalysts. The reaction proceeds via an aryl palladium complex formed by transmetallation reaction between catalyst and Ar₃Bi. The whole synthetic transformation has high atom economy as all three aryl groups attached to bismuth are efficiently transferred to the electrophilic partner.     

Design,Synthesis, and Biological Activities of Novel 2‐Alkylpyrrole Derivatives

To investigate the alkyl analog of insecticide chlorfenapyr, two series of 2‐alkyl‐4‐bromo‐5‐(trifluoromethyl)pyrrole‐3‐carbonitriles were synthesized with a cycloaddition as the key step. The target products were characterized by ¹H‐NMR spectroscopy, elemental analysis, or HRMS. The insecticidal, herbicidal, and antifungal activities of the target compounds were evaluated and found that these compounds did not show much insecticidal activity, but compounds 4 , 10 , and 11 had very good fungicidal activities against Alternaria solani and Fusarium oxysporum. Moreover, compound 4 had an outstanding inhibition effect against pigweed.     

Synthesis and Antifungal Activity Evaluation of Novel Substituted Pyrimidine‐5‐Carboxamides Bearing the Pyridine Moiety

A series of novel N‐(substituted phenyl/benzyl)‐2‐methylthio‐4‐((pyridin‐3‐ylmethyl)amino)pyrimidine‐5‐carboxamides were synthesized by multistep reactions. The structures of the target compounds were characterized by IR, ¹H NMR, ¹³C NMR, and elemental analysis. Their in vitro antifungal activities against two kinds of plant pathogenic fungi were evaluated by the mycelial growth rate method. The result showed that at the dosage of 100 μg/mL, several of these compounds exhibited moderate activity against Botrytis cinerea with inhibition rates of ~70%, and most compounds (e.g., 5a , 5c , 5e , 5f, and 5h ) possessed excellent activity against Sclerotinia Sclerotiorum with more than 90% inhibition rate.     

Synthesis,Characterization, and Biological Evaluation of Novel 3‐(4‐Chlorophenyl)‐2‐(substituted)quinazolin‐4(3H)‐one Derivatives as Multi‐target Anti‐inflammatory Agents

A novel class of 3‐(4‐chlorophenyl)‐2‐(substituted)quinazolin‐4(3H)‐one derivatives were synthesized, and the structure of synthesized compounds was characterized by IR, ¹H NMR, and mass spectroscopy. The newly synthesized compounds ( 4a–g and 6a–g ) were tested for their in vitro cyclooxygenase (COX) inhibition activity. The compounds have inhibitory profile against both COX‐1 and COX‐2, and some of the compounds are found to be selective against COX‐2. The compound 6g showed distinct inhibitory activity on COXs. The synthesized compounds were evaluated for their potential anti‐inflammatory activity as inhibitors of the proinflammatory cytokines IL‐6. Compounds 4d – g showed the highest level of inhibition among all the tested compounds. Thus, our data suggested that these compounds may represent a new class of potent anti‐inflammatory agents.     

Synthesis,characterization and α‐amylase and α‐glucosidase inhibition studies of novel vanadyl chalcone complexes

A series of chalcone ligands and their corresponding vanadyl complexes of composition [VO (L^I–IV)₂(H₂O)₂]SO₄ (where L^I = 1,3‐Diphenylprop‐2‐en‐1‐one, L^II = 3‐(2‐Hydroxy‐phenyl)‐1‐phenyl‐propenone, L^III = 3‐(3‐Nitro‐phenyl)‐1‐phenyl‐propenone, L^IV = 3‐(4‐Methoxy‐phenyl)‐1‐phenyl‐propenone) have been synthesized and characterized using various spectroscopic (Fourier‐transform infrared, electrospray ionization mass, nuclear magnetic resonance, electron paramagnetic resonance, thermogravimetric analysis, vibrating sample magnetometer) and physico‐analytic techniques. Antidiabetic activities of synthesized complexes along with chalcones were evaluated by performing in vitro and in silico α‐amylase and α‐glucosidase inhibition studies. The obtained results displayed moderate to significant inhibition activity against both the enzymes by vanadyl chalcone complexes. The most potent complexes were further investigated for the enzyme kinetic studies and displayed the mixed inhibition for both the enzymes. Further, antioxidant activity of vanadyl chalcone complexes was evaluated for their efficiency to release oxidative stress using 2,2‐diphenyl‐1‐picryl‐hydrazyl‐hydrate assay, and two complexes (Complexes 2 and 4 ) have demonstrated remarkable antioxidant activity. All the complexes were found to possess promising antidiabetic and antioxidant potential.     

Screen‐Printed Disposable Sensors Modified with Bismuth Precursors for Rapid Voltammetric Determination of 3 Ecotoxic Nitrophenols

This work reports the application of screen‐printed electrodes bulk‐modified with bismuth precursors to the voltammetric determination of 2‐nitrophenol (2‐NP), 4‐nitrophenol (4‐NP) and 2,4‐dinitrophenol (2,4‐DNP) in water samples. A bismuth film was formed at the electrode surface via in situ reduction of the precursor compound contained in the electrode matrix by cathodic polarization at ?1.20 V. The formation of bismuth layer at the precursor‐modified electrodes was assessed by cyclic voltammetric (CV) at different pH values and by optical techniques. The target nitrophenols were voltammetrically determined by recording their reduction peaks in the differential pulse (DP) mode. The composition and content of the precursor compounds in the printed ink and the effect of the pH of the supporting electrolyte on the DP reduction currents of the 3 target nitrophenols were studied. The limits of quantification (LOQs) in three water matrices (distilled water, tap water and surface water) were in the range 1.1–2.2 µmol L^?1_. Using a simple solid‐phase extraction (SPE) procedure with Lichrolut EN cartridges and elution with methanol, a preconcentration factor of 100 was achieved; the LOQs were 0.021, 0.027 and 0.025 µmol L^?1 for 2‐NP, 4‐NP and 2,4‐DNP, respectively. The recoveries of samples spiked with the 3 target nitrophenols at two concentration levels (0.04 and 0.1 µmol L^?1) were always >87 %.     

NHC–Silver(I) Complexes as Chemical Nucleases; Synthesis,Crystal Structures,and Antibacterial Studies

A series of N‐heterocyclic carbene (NHC) precursors, 1‐methoxylethyl‐3‐allylimidazolium hexafluorophosphate ( 1 ), 1‐ethyl‐3‐allylimidazolium hexafluorophosphate ( 2 ), and 1‐pentyl‐3‐allylimidazolium hexafluorophosphate ( 3 ) were synthesized. These salts were treated with Ag₂O to afford their corresponding mononuclear Ag(I)‐NHC complexes, namely 1‐methoxylethyl‐3‐allylimidazolium silver(I) hexafluorophosphate ( 4 ), 1‐ethyl‐3‐allylimidazolium silver(I) hexafluorophosphate ( 5 ), and 1‐pentyl‐3‐allylimidazolium silver(I) hexafluorophosphate ( 6 ), respectively. These compounds were characterized by physicochemical and spectroscopy techniques. Compounds 4 and 5 were structurally characterized by single crystal X‐ray diffraction, and their stability in solution was investigated and found to be acceptable for the antibacterial studies. These new NHC precursors and their respective Ag–NHC complexes were screened for their antibacterial activities against Staphylococcus aureus (ATCC 12600) and Escherichia coli (ATCC 25922). Compounds 1–3 showed no inhibition, whereas 4–6 inhibited the growth of these bacteria. The nuclease activities of the reported compounds against plasmid DNA and RNA were assessed by gel electrophoresis, and the results indicate that complexes 5 and 6 can degrade both DNA and RNA in the absence of an oxidant.     

Synthesis and Antimicrobial Activity of Some New N‐substituted‐5‐arylidene‐thiazolidine‐2,4‐diones

A total of 17 new N‐substituted derivatives ( 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j , 2k and 3b , 3c , 3d , 3e , 3f , 3g , 3h ) of 5‐((2‐phenylthiazol‐4‐yl)methylene) thiazolidine‐2,4‐dione ( 2a ) and 5‐(2,6‐dichloro‐ benzylidene)thiazolidine‐2,4‐dione ( 3a ) were synthesized. The structural elucidation of the newly synthesized compounds was based on elemental analysis and spectroscopic data (MS, ¹H NMR, ¹³C NMR), and their antimicrobial activities were assessed in vitro against several strains of Gram‐positive and Gram‐negative bacteria and one fungal strain (Candida albicans) as growth inhibition diameter. Some of them showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus, Bacillus cereus, and Enterococcus fecalis bacterial strains, whereas almost all the compounds were inactive against Listeria monocytogenes. All of the synthesized compounds showed moderate to very good activity against C. albicans.     

Synthesis,Characterization, and Investigation of Cholinesterase Inhibitory Properties of Novel Phthalocyanines

In this study, 4‐{2‐(2‐thienyl)ethoxy}phthalonitrile ( 3 ) and its tetra substituted peripherally metal‐free ( 4 ), lead (II) ( 5 ), magnesium (II) ( 6 ), and cobalt (II) ( 7 ) phthalocyanines were synthesized. The structural characterization of the obtained compounds was performed by a combination of FTIR, ¹H‐NMR, UV–vis, and MALDI‐TOF techniques. The inhibitory properties of these compounds were determined using Ingkaninan's methods against cholinesterase enzymes. Compound ( 7 ) had the highest enzyme inhibitory effect toward AChE and BuChE enzymes with IC₅₀ values of 23.71 ± 0.39 and 27.29 ± 0.22 μM, respectively. The enzyme kinetic study of compound ( 7 ) demonstrated noncompetitive AChE inhibition and uncompetitive BuChE inhibition. The K_i values of compound ( 7 ) against AChE and BuChE were found to 39.15 and 7.25 μM, respectively. In the tested compounds, ( 7 ) deserves further investigation for potential therapeutic candidates of Alzheimer's disease.     

Synthesis,spectral characterization,and biological evaluation of imidazole‐substituted pyridine‐2‐amine and benzo‐substituted imidazole‐2‐amine

A series of new imidazole‐substituted pyridine‐2‐amine and benzo‐substituted imidazol‐2‐amine 3 – 12 were synthesized by treating various amines 1(a – d) with alkyl/aryl isothiocyanate 2(a‐c) at 60–90°C in isopropyl alcohol without using any catalyst with high yields. The structures of all the newly synthesized compounds were characterized using IR, NMR (¹H, ¹³C), mass, and elemental analyses. All the newly synthesized compounds were screened for their in vitro antioxidant and antimicrobial activities to understand their biological potency. All the title compounds exhibited good antioxidant and antimicrobial activities in vitro when compared to the standard drugs.     

Synthesis and Urease Inhibition Studies of Barbituric and Thiobarbituric Acid Derived Sulphonamides

Various novel barbituric and thiobarbituric acid derived sulphonamides were synthesized in excellent yield via three components single pot reaction; and these were screened for in vitro urease inhibition studies against jack bean urease. The compounds 1‐7 were found to exhibit a low to moderate activity whereas compounds 8‐14 showed a significant activity (88.3‐99.9% inhibition determined at 500 μM concentration). Structures of the synthesized compounds were confirmed by ¹H‐NMR, ¹³C‐NMR, mass spectrometry and elemental analysis data.     

Synthesis,In Vitro Biological Screening,and In Silico Computational Studies of Some Novel Imidazole‐2‐thiol Derivatives

Substituted imidazole analogues 2‐((5‐acetyl‐4‐methyl‐1‐phenyl‐1H‐imidazole‐2‐yl)thio)‐N‐phenylacetamides ( 3a – 3m ) have been synthesized from 1‐[1‐(phenyl)‐2‐mercapto‐4‐methyl‐1H‐imidazol‐5‐yl]‐ethanone ( 1a – 1e ) and 2‐chloro‐N‐phenylacetamide ( 2a – 2i ) in the presence of potassium carbonate as a catalyst in dimethylformamide under microwave irradiation as well as conventional method. Structures of the obtained compounds have been confirmed by advance spectroscopic techniques such as IR, ¹H NMR, ¹³C NMR, and mass spectrometry. All the synthesized compounds were tested for their in vitro antimicrobial and antituberculosis activities. Good antibacterial molecules were further screened for the bacterial resisted cell line, from which compound 3b shows maximum inhibition. In silico molecular docking study was carried out to discover the binding affinity of synthesized compounds with active site of transferase (PDB ID: 1HNJ) and antibiotic resistance (PDB ID: 1W3R) protein. Moreover, molecular dynamics study of the 3b ‐1W3R complex has also been performed, as 3b has a good antibacterial activity as compared with other.     

Synthesis and Pharmacological Evaluation of Some New Chromeno[3,4‐c]pyrrole‐3,4‐dione‐based N‐Heterocycles as Antimicrobial Agents

The reaction of 2‐oxo‐2H‐chromene‐3‐carboxamide ( 1 ) with carbon disulfide afforded 1‐mercaptopyrrolo[3,4‐c ]chromene‐3,4‐dione ( 3 ). The latter compound was utilized as versatile building block for new azole systems via incorporating in a series of manipulations including cyclocondensation reactions. The structure of the newly synthesized compounds has been confirmed by IR, ¹H NMR, ¹³C NMR, mass spectral, and elemental analysis. Furthermore, some selected compounds were screened in vitro for their antimicrobial activities. The results declared that most of the synthesized compounds have high antimicrobial activity.