Bis-Thiourea Bearing Aryl and Amino Acids Side Chains and Their Antibacterial Activities

Abstract

A series of symmetrical 1,3-bis thiourea 1a–e and 1,4-bis thiourea derivatives 2a–e have been successfully synthesized from the reactions of amines with 3-acetylbenzoyl isothiocyanate and 4-acetylbenzoyl isothiocyanate, respectively. All the synthesized compounds were characterized by FT-IR spectroscopy and ¹H and ¹³C NMR spectroscopy. The compounds were screened for their antibacterial activity by turbidimetric method using gram-negative bacteria (E. coli ATCC 8739) using turbidimetric method. The newly synthesized bis-thiourea derivatives bearing aryl side chains showed good antibacterial activity against E. coli. The effect of the molecular structure of the synthesized compounds on the antibacterial activity is discussed.     

N‐Glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea Derivatives: Potential Anti‐TB Therapeutic Agents

Thiocarlide (THC; N,N′‐bis[p‐(isoamyloxy)phenyl]‐thiourea; also known as Isoxyl^®) has been used in the past as an anti‐tuberculosis agent. In an effort to improve the therapeutic value of THC, several N‐glycosyl‐N′‐[p‐(isoamyloxy)phenyl]‐thiourea derivatives were synthesized by coupling an aniline derivative and glycosyl isothiocyanates. The minimum inhibitory concentration (MIC) values of the new products against M. tuberculosis were determined.     

Synthesis,biological screening,in silico study and fingerprint applications of novel 1, 2, 4-triazole derivatives

A series of novel 1,2,4 triazole derivatives were synthesized by treating 4-bromo-2-(4H-1,2,4-triazole-3-yl)aniline (4) with different substituted benzene sulfonyl chlorides 5(a-f) and benzyl bromides 7(a-e) . IR, ¹H-NMR, ¹³C-NMR, and mass analysis confirmed the structures of the newly synthesized compounds. All derivatives were screened for their in vitro antibacterial activity against two bacterial strains viz Escherichia coli and Staphylococcus aureus, antifungal activity against Aspergillus flavus and Candida albicans, anthelmintic activity against Pheretima posthuma and also cytotoxicity activity against MDA-MB 231 and A375 cancer cell lines. It was found that some of the derivatives showed significant antibacterial, antifungal, anthelmintic, and cytotoxic activities when compared to respective standard drugs. Molecular docking studies have assisted the theoretical binding mode of the target molecules. Compounds were also explored for fingerprint application.     

Design and Synthesis of Novel Thioureas Derived from 4‐(4‐Fluorophenoxy)aniline as Anticancer Agents

A new series of thiourea derivatives were obtained by the reaction of 4‐(4‐fluorophenoxy) aniline with different isothiocyanates. Their chemical structures were confirmed by ultraviolet (UV ), infrared (IR ), nuclear magnetic resonance (NMR ), and mass spectral data and elemental analysis. All the synthesized thiourea derivatives were evaluated for their in vitro cancer activity against the human breast cancer cell lines MCF ‐7 (human breast adenocarcinoma) and SKBr ‐3 (human epithelial breast adenocarcinoma). Most of the derivatives exhibited significant anticancer activity. Especially, compound 3 showed the most potent activity (IC₅₀ 20.1 μM ) against SKBr ‐3 when compared with the drugs 5‐fluorouracil and cisplatin, and, most importantly, it did not affect normal breast epithelial cells (4010).     

Synthesis and Antimicrobial Studies of Some Quinolinylpyrimidine Derivatives

The quinolinylpyrimidine derivatives were prepared by the condensation of quinolinyl chalcones with urea (or thiourea) under basic conditions by using both conventional and microwave heating. Their IR, ¹H NMR, ¹³C NMR, mass spectra and CHN analyses confirmed the prepared compounds. The newly prepared quinolinylpyrimidine derivatives were screened for antimicrobial activities against the bacterial strains viz. S. aureus, Shigella, Salmonela, P. aeroginosa, B. Subtilus and E. coli and found considerably active against S. aureus, P. aeroginosa and E. coli.     

Microwave‐assisted Synthesis,Characterization, and Density Functional Theory Study of Biologically Active Ferrocenyl Bis‐pyrazoline and Bis‐pyrimidine as Organometallic Macromolecules

Organometallic macromolecules such as ferrocenyl bis‐pyrazoline ( 2 , 3 ) and bis‐pyrimidine ( 4 , 5 ) derivatives were synthesized by reacting ferrocenyl bis‐chalcone 1 with thiosemicarbazide/phenylhydrazine/guanidine hydrochloride/thiourea, respectively, under microwave irradiation. Ferrocenyl bis‐chalcone 1 was synthesized by reacting acetyl ferrocene with terephthalaldehyde. Synthesized compounds were characterized by using IR, ¹H NMR, ¹³C NMR, EI‐MS, and elemental analysis. In vitro antibacterial activity against two Gram‐negative and two Gram‐positive bacteria was determined by the disc diffusion assay. Moreover, minimum inhibition concentrations were also measured with reference to chloramphenicol. Thioamide functionally containing ferrocenyl bis‐pyrazoline derivative 2 shows the best antibacterial activity on Escherichia coli and Salmonella typhimurium, among all tested compounds including the reference drug chloramphenicol. The structure–activity relationship is also developed by using computational calculations with density functional theory (DFT)/B3LYP method.     

Synthesis,Characterization, and Antibacterial Activity of Some Novel Substituted Imidazole Derivatives via One‐pot Three‐Component

A simple and highly efficient one‐pot, three‐component synthesis of novel substituted imidazole derivatives has been reported by the reaction of 3‐(2‐bromoacetyl)‐2H‐chromen‐2‐one, ammonium thiocyanate, and phenacyl aniline in the presence of acetic acid as a solvent under reflux condition with good yields. The structures of newly synthesized compounds were characterized by their analytical and spectral data. One of these compounds 4a showed good antibacterial activity against Escherichia coli gram‐negative strains.     

Synthesis,antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives

We describe the synthesis of some novel p-tert-butylcalix[4]arene-based (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives ( 4a–e ). These compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene ( 1 ) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate ( 3a–e ) in the presence of potassium carbonate as a weak base and dry acetone as the solvent. All the newly synthesized calix[4]arene derivatives were characterized by elemental analysis and various spectroscopic methods such as FT-IR, ¹H NMR,¹³C NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for their antibacterial and antifungal activities against Escherichia coli and Aspergillus fumigates in comparison with enrofloxacin and amphotericin as reference drugs, which are normally used for treating such infections. The synthesized compounds showed different inhibition zones against the tested bacteria and fungi. Compound 4c was found to be most effective against A. fumigates, whereas compound 4e was found to be equally effective against E. coli and A. fumigates.     

Synthesis of New Triazole and Oxadiazole Derivatives of Quinazolin‐4(3H)‐one and Their Antimicrobial Activity

A series of new triazole derivatives of quinazolin‐4(3H)‐one and new oxadiazole derivatives of quinazolin‐4(3H)‐one were synthesized. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. All the newly synthesized compounds were screened for antibacterial activity against Staphylococcus aureus, Bacillus subtilis (gram‐positive bacteria), Escherichia coli, Pseudomonas aeruginosa (gram‐negative bacteria), and antifungal activity was carried out against Candida albicans and Aspergillus niger.     

Synthesis and Antimicrobial Evaluation of Some Chalcones and Their Derived Pyrazoles,Pyrazolines, Isoxazolines,and 5,6-Dihydropyrimidine-2-(1<Emphasis Type="Italic">H</Emphasis>)-thiones

Summary. Chalcones were synthesized by a base catalyzed Claisen-Schmidt condensation reaction. Bromination of chalcones afforded the dibromo derivatives. Monobromo derivatives could be obtained by treating the corresponding dibromochalcones with dry benzene in the presence of triethylamine. Pyrazole derivatives were obtained by refluxing of dibromochalcones with phenylhydrazine or 2,4-dinitrophenylhydrazine in dry pyridine. Chalcones were treated with hydrazine hydrate or phenyl hydrazine in ethanol to afford Δ ²-pyrazolines and N-phenyl-Δ ²-pyrazolines. Condensation of chalcones with hydroxylamine hydrochloride or thiourea in ethanolic sodium hydroxide solution gave 4,5-dihydroisoxazoles and 5,6-dihydropyrimidine-2-(1H)-thiones. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.     

Synthesis and Antimicrobial Evaluation of Some Chalcones and Their Derived Pyrazoles, Pyrazolines, Isoxazolines, and 5,6-Dihydropyrimidine-2-(1 H )-thiones

Chalcones were synthesized by a base catalyzed Claisen-Schmidt condensation reaction. Bromination of chalcones afforded the dibromo derivatives. Monobromo derivatives could be obtained by treating the corresponding dibromochalcones with dry benzene in the presence of triethylamine. Pyrazole derivatives were obtained by refluxing of dibromochalcones with phenylhydrazine or 2,4-dinitrophenylhydrazine in dry pyridine. Chalcones were treated with hydrazine hydrate or phenyl hydrazine in ethanol to afford Δ ²-pyrazolines and N-phenyl-Δ ²-pyrazolines. Condensation of chalcones with hydroxylamine hydrochloride or thiourea in ethanolic sodium hydroxide solution gave 4,5-dihydroisoxazoles and 5,6-dihydropyrimidine-2-(1H)-thiones. The prepared compounds were tested for antimicrobial activity against four different bacterial species displaying different degrees of antibacterial activities or inhibitory actions.     

Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis,characterization, antimicrobial activity and docking studies

Abstract

An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, ¹H NMR, ¹³C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 µg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8?kcal/mol) with no adverse effect in the active site of protein.     

Synthesis,Characterization, and Spectroscopic Properties of Hexa(4-Bromo-2-Formyl-Phenoxy)Cyclotriphosphazene and Hexa(4-Chloro-2-Formyl-Phenoxy)Cyclotriphosphazene and Fully Substituted Cyclotriphosphazene Derivatives Bearing a Schiff Base at Room Temperature

Abstract

Hexa(4-bromo-2-formyl-phenoxy)cyclotriphosphazene (2) and hexa(4-chloro-2- formyl-phenoxy)cyclotriphosphazene (3) were obtained from the reactions of hexachloro- cyclotriphosphazene (1) with 5-bromosalicylaldehyde and 5-chlorosalicylaldehyde in the presence of (C₂H₅)₃N and K₂CO₃ at room temperature, respectively. The new two organocyclotriphosphazenes bearing formyl groups were reacted with 4-cyano aniline, 2-phenyl aniline, 4-aceto aniline, 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, 2-(4-morpholino)ethyl amine, 4-carboxy aniline, 4-carbomoyl aniline, 2-mercapto aniline, and 5-amino isoquonoline to prepare cyclotriphosphazene derivatives containing a Schiff base at room temperature. However, fully phenoxy-substituted cyclotriphosphazenes containing a Schiff base were isolated from the reactions of the compound 2 and 3 with 5-chloro-2-hydroxy aniline, 2-hydroxy aniline, 4-hydroxy aniline, and 2-(4-morpholino)ethyl amine. The structures of the synthesized compounds were characterized by elemental analysis, IR, and NMR (¹H, ¹³C, ³¹P) spectroscopy. According to the results of the analysis, all synthesized compounds were found to be fully substituted organocyclotriphosphazenes, such as hexa[4-bromo-2-(5-chloro-2-hydroxy-pheyliminomethyl)phenoxy]cyclotriphosphaze (2a). All cyclotriphosphazene derivatives synthesized gave fluorescence emission peaks in range between 300 nm and 410 nm.     

Synthesis and Structure of Novel 4‐Arylamino‐2‐phenyl‐6‐substituted‐quinazoline

A series of quinazoline derivatives were synthesized via the cyclization of N, N′–disubstituted thiourea derivatives in the mixed solvent of acetontrile and aqueous NaOH by ultraviolet light irradiation. All the compounds are characterized by IR, ¹HNMR, ¹³CNMR, MS, and element analysis. The absolute configurations of 3a was determined by X‐ray crystallography.     

Synthesis and antimicrobial activity of tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives

Abstract  

A series of new tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives were synthesized for the first time via tetrazolo[1,5-a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectral data were used to elucidate the structures of all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds were investigated against Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and two fungi, Candida albicans and Aspergillus niger, in comparison with standard drugs. Some of the tested compounds showed significant antimicrobial activity.     

A facile synthesis of novel 5‐substituted pyridine 2 carboxamide derivatives and their biological evaluation and 3D QSAR studies

A variety of novel 5‐substituted pyridine 2 carboxamides were designed and synthesized using both normal and solvent‐free microwave (MW) irradiation techniques. The results revealed that MW protocol proceeded smoothly under mild reaction conditions in short reaction times, thus avoiding the use of toxic organic solvents. Structural elucidation of the synthesized compounds was carried out on the basis of various spectroscopic methods, such as ¹H NMR, ¹³C NMR, LCMS, and IR. The synthesized compounds were evaluated for their in vitro antimicrobial activity (MIC) using the agar disk diffusion method. Among the various synthetic compounds, compound 3b showed higher potential activity against Escherichia coli than the other compounds. The order of activity against E. coli of the studied compounds is 3b > 3e > 3g > 3h > 3d > 3c > 3a > 3f . Additionally, 2D and 3D structural features of the synthesized derivatives were recognized by the 3D‐QSAR model. This validated model exhibited good internal (r², 0.924) and external prediction (r²pred, 0.851) correlation. The results of QSAR studies concluded that Alog P, the number of hydrogen bond acceptors, and the number of rotatable bonds were necessary features for the activity of the pyridine carboxamide derivatives.     

Synthesis and Antimicrobial Studies of Organophosphates Derived From 2-(2″-Hydroxynaphthyl)Benzoxazole

Abstract

A series of biologically active phenoxy derivatives of 2-substituted benzoxazole organophosphates have been synthesized by the reaction of O-(naphthyl benzoxazolyl-2-) phosphorodichloridate/phosphorodichloridothioate with phenol/4-chlorophenol/4-nitroph- enol in 1:1 and 1:2 molar ratios. These compounds have been characterized on the basis of elemental analysis, IR, ¹H NMR, ³¹P NMR, and mass spectral studies. The antibacterial activity of these 2-substituted benzoxazole phenoxy derivatives has been evaluated against pathogenic bacteria Staphylococcus aureus (+ve) and Escherichia coli (?ve). The antifungal activity of these 2-substituted benzoxazole phenoxy derivatives has been evaluated against pathogenic fungi Aspergillus niger and Fusarium oxysporium. All compounds were found to have significant antibacterial and antifungal activity.     

Synthesis and In Vitro Antimicrobial Activity of 1,3,4‐Oxadiazole‐2‐thiol and its Analogs

The present communication deals with the synthesis of 1,3,4‐oxadiazole‐2‐thiol derivatives containing cyclic secondary amines such as morpholine, N‐methyl piperizine, and piperizine. The structural elucidation is based on the spectral data (IR, ¹H NMR, and ¹³C NMR) .The newly synthesized compounds were then tested for their antimicrobial activity against a representative panel of micro‐organisms such as Bacillus subtilis, Escherichia coli and Candida albicans by using ciprofloxacin and fluconazole as reference drugs for bacteria and fungi, respectively. These synthesized compounds showed moderate to potential antibacterial and antifungal activity in the range of 6–50 μM against the selected bacteria and 12–50 μM against the most common fungi, respectively.     

Synthesis,Docking, ADME‐Tox Study of 2‐(2‐(2‐Chlorophenyl)quinoline‐4‐carbonyl)‐N‐substituted hydrazinecarbothioamide Derivatives and Their Biological Evaluation

A series of 2‐(2‐(2‐chlorophenyl)quinoline‐4‐carbonyl)‐N‐substituted hydrazinecarbothioamide derivatives were synthesized by facile and efficient conventional method. The structures of the compounds were elucidated with the aid of an elemental analysis, IR, ESI‐MS, ¹H‐NMR, and ¹³C‐NMR spectral data. The synthesized compounds were evaluated for their in vitro antibacterial, antifungal, antimalarial, and antituberculosis activity against standard drugs. The bacterial studies were determined against gram‐positive and negative bacteria. These compounds were found to a broad spectrum of activity against the screened bacteria, but poor activity was observed against Pseudomonas aeruginosa and Escherichia coli. Compounds 8d , 8f , 8i , 8l , and 8n showed the potent activity against Staphylococcus aureus. Compounds 8d , 8g , 8k , 8l , and 8q show the potent activity against antimalarial as compared with the standard drugs Chloroquine, Quinine and compounds 8h , 8n , and 8o shows mild activity against H37Rv strain. Molecular docking revealed that synthesized derivatives and target proteins were actively involved in a binding pattern and had a significant corelation with biological activity. We have also performed a molecular dynamics and ADME‐Tox parameters for the synthesized compounds.     

Synthesis of New Pyrimidine,Quinazoline and Diazatricyclo Derivatives by Multicomponent Reaction and Evaluation of Their Biological Activity

Abstract

A series of new pyrimidine and quinazoline derivatives was synthesized by a Biginelli-like reaction of urea/thiourea, aldehyde, and ketone in the presence of hydrochloric acid as a catalyst. In a similar way, some novel diazatricyclo derivatives were obtained via a Biginelli-like reaction followed by an intramolecular Michael-type addition. The yields of products were reasonable after recrystallization from ethanol. All newly synthesized compounds were characterized using IR and NMR (¹H and ¹³C) spectroscopy and elemental analysis. The antibacterial activity of these compounds was investigated against Staphylococcus aureus (RTCC, 1885), and Escherichia Coli (ATCC, 35922).

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