Preparation,structure elucidation,and antioxidant activity of new bis(thiosemicarbazone) derivatives

Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, ¹H NMR, ¹³C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate the identification of the synthesized molecules. The in vitro antioxidant activity of the synthesized compounds was analysed with the 1,1-diphenyl-2-picryl hydrazyl free-radical–trapping process. The synthesized compounds exhibited lower antioxidant activity than the standard ascorbic acid. IC₅₀ values of the synthesized molecules measured from 3.81 ± 0.01 to 29.05 ± 0.11 μM. Among the synthesized compounds, compound 3 had the best antioxidant activity. Moreover, this study explained the structure–activity relationship of the synthesized molecules with different substituents in radical trapping reactions.     

Facile Synthesis of 3,6‐Disubstituted‐1,2,4‐triazolo‐[3,4‐b]‐1,3,4‐thiadiazoles via Oxidative Cyclization of n‐Heteroaryl‐Substituted Hydrazones and Their Biological Activity

Fused 3,6‐disubstituted triazolothiadiazoles were synthesized in good yield from a rapid and convenient oxidative cyclization of N‐heteroaryl‐substituted hydrazones promoted by chloramine‐T trihydrate at ambient temperature. The structure of the synthesized compounds was confirmed by FTIR, ¹H NMR, ¹³C NMR, and mass spectral data. The synthesized compounds were evaluated for their antioxidant and antitubercular activities. All the compounds 5a‐i and 6a‐i showed good antitubercular activity. However, only compounds 5a‐i showed good antioxidant activity.     

Synthesis,spectroscopic studies,and antioxidant activities of novel thio/carbohydrazones and bis-isatin derivatives from terephthalaldehyde

New bis(isatins-thio/carbohydrazones) based on Schiff bases were prepared from terephthalaldehyde biscarbohydrazone and 5-substituted isatins in the presence of a drop of sulfuric acid under reflux in ethanol. Terephthalaldehyde bis(thio/carbohydrazone) was synthesized by the reaction of (thio)/carbohydrazide and terephthalaldehyde in the presence of a few drops of acetic acid under reflux in ethanol. The structures of these synthesized compounds were determined using IR, ¹H NMR, and ¹³C NMR spectroscopy and elemental analysis. The in vitro antioxidant activity of all the compounds was determined by the 1,1-diphenyl-2-picryl hydrazyl (DPPH.) free radical scavenging method. Compound 2 showed the best antioxidant activity.     

Design,Synthesis, Antimicrobial,and Antioxidant Activity of Dimers of Chromene Containing 1,2,3-Triazole Derivatives Bearing an Alkyl Spacer

A new series of chromene based 1,2,3-triazole derivatives has been synthesized by incorporating biologically active heterocyclic rings containing chromene and triazole moieties in one molecular structure. All newly synthesized compounds are characterized by ¹H and ¹³C NMR, mass, and IR spectra. The title compounds are tested for their activity against different bacterial and fungal strains, and antioxidant activity. Several compounds are determined to be potent antimicrobial and antioxidant agents.

     

Synthesis,design, and antimicrobial activity of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinones based on quinoline derivatives

The pyrido[2,3-d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti-inflammatory. Hence, we synthesized an efficient new series of 2-thioxo-pyrido[2,3-d]pyrimidinone, 2-hydrazinyl-(quinolin-2-yl)pyrido[2,3-d]pyrimidinone,N′-(quinolin-2-yl)-pyrido[2,3-d]pyrimidine-(formo/aceto)-hydrazide and substituted-(quinolin-2-yl)pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline-pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design.     

An efficient one-pot synthesis of coumarin-amino acid derivatives as potential anti-inflammatory and antioxidant agents

Abstract

A series of seven coumarinyl-amino acid ester conjugates have been synthesized and characterized by NMR (¹H and 13C) and mass spectra. Further, the compounds were investigated for their therapeutic applications such as anti-inflammatory and antioxidant activities. Among the synthesized compounds most of the analogs showed good efficiency compared with the standard.     

Synthesis of Novel Benzofuran‐Gathered C‐2,4,6‐substituted Pyrimidine Derivatives Conjugated by Sulfonyl Chlorides: Orally Bioavailable,Selective, Effective Antioxidants and Antimicrobials Drug Candidates

In the present study, we have made an effort to develop the novel synthetic antioxidants and antimicrobials with improved potency. The novel benzofuran‐gathered C‐2,4,6‐substituted pyrimidine derivatives 5a , 5b , 5c , 5d , 5e , 5f , 6a , 6b , 6c , 6d , 6e , 6f , 7a , 7b , 7c , 7d , 7e , 7f , 8a , 8b , 8c , 8d , 8e , 8f , 9a , 9b , 9c , 9d , 9e , 9f were synthesized by simple and efficient four‐step reaction pathway. Initially, o‐alkyl derivative of salicylaldehyde readily furnish corresponding 2‐acetyl benzofuran 2 in good yield, upon the treatment with potassium tertiary butoxide in the presence of molecular sieves. Further, Claisen–Schmidt condensation with aromatic aldehydes via treatment with thiourea followed by coupling reaction with different sulfonyl chlorides afforded target compounds. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis and further screened for their antioxidant and antimicrobial activities. The results showed that the synthesized compounds 8b , 8e , 9b , and 9e produced significant antioxidant activity with 50% inhibitory concentration higher than that of reference, whereas compounds 7d and 7c produced dominant antimicrobial activity at concentrations 1.0 and 0.5 mg/mL compared with standard Gentamicin and Nystatin, respectively.     

Ultrasound‐assisted Synthesis of Novel Pyrazole and Pyrimidine Derivatives as Antimicrobial Agents

Herein, we report a convenient and facile methodology for the synthesis of new series of pyrazole and pyrimidine derivatives 2a – f and 3a – f under ultrasound irradiation. Pyrazole and pyrimidine derivatives have been synthesized in better yields and shorter reaction times compared with the conventional method. The chemical structures of all the synthesized compounds were elucidated by their IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. Further, the target compounds were screened for their antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and two fungi (Candida albicans, Aspergillus niger). In particular, compounds 2a , 2d , 2e , 3a , 3e , and 3f exhibited potent antimicrobial activity.     

Derivational,Structural, and Biological Studies of Some New Pyrazolyl,Isoxazolyl, Pyrimidinyl,Pyridazinyl, and Pyridopyridazinyl from 4‐Substituted Antipyrine

(1,5‐Dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbono‐hydrazonoyl dicyanide was used as a key intermediate for the synthesis of novel pyrazole, isoxazole, pyrimidine, and pyridazine derivatives. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). The compounds were tested for their in vitro antibacterial activity against Gram‐positive bacteria as (Staphylococcus aureus and Bacillus subtilis ) and Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ). The investigated compounds were tested against two strains of fungi Botrytis fabae and Fusarium oxysporum using diffusion agar technique. The biological results showed clearly that most of the synthesized compounds revealed mild to moderate activity against the used microorganisms.     

Synthesis and Antimicrobial Activity of Some Novel Hydrazide,Pyrazole, Triazine,Isoxazole, and Pyrimidine Derivatives

In continuation of our efforts to find a new class of antimicrobial agents, a series of pyrazole, 1,2,4‐triazine, isoxazole, pyrimidine, and other related products containing a hydrazide moiety were prepared via the reaction of 2‐cyano‐N‐((2‐methoxynaphthalen‐1‐yl)methylene) acetohydrazide ( 1 ) with appropriate chemical reagents. These compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration against most of test organisms was performed. Among the tested compounds 4 , 5 , 6 , and 16 displayed excellent antimicrobial activity. All the synthesized products were confirmed by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data.     

Synthesis,characterization, DNA binding,antibacterial, and antioxidant activity of new bis-phthalimides

New bis-phthalimides were synthesized by 2: 1 condensation of phthalic anhydride and tetrachlorophthalic anhydride with 1,2,4-triazole-3,5-diamine, pyridine-2,6-diamine, and 4-hydroxypyrimidine- 2,6-diamine. The synthesized compounds were characterized by elemental analyses and IR, ¹H NMR, and mass spectra. Their interaction with calf thymus DNA (ct-DNA) was studied by UV-Vis spectrophotometry, cyclic voltammetry, and viscosity measurements, which revealed intercalative mode of binding to ct-DNA. Antibacterial activity of the synthesized compounds against Escherichia coli and Streptococcus mutans was assessed in vitro by the agar well diffusion method. The antioxidant activity of these compounds was estimated by DPPH assay.     

Design,Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α‐(Benzoylamino)‐β‐substituted Acrylic Amide Derivatives of Pyrazolo[1,5‐a]pyrimidine

A novel series of α‐(benzoylamino)‐β‐substituted acrylic amide derivatives of pyrazolo[1,5‐a]pyrimidine has been synthesized using a convergent multistep synthesis. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR, ESI‐MS, and IR analyses. Those new compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of nine derivatives synthesized in the current study, compounds 13g , 13d , 13h , and 13i exhibited the greatest anticancer activities in HeLa and HepG₂ cell lines. The in vitro anticancer activity of compound 13g against HeLa, HepG₂, and MCF‐7 cell lines is superior to the marketed drugs paclitaxel and SAHA.     

Synthesis,characterization and antioxidant activity of bis (arylsulfonylmethyl/arylaminosulfonylmethylazolyl) pyridines

A new class of bis(arylsulfonylmethylazolyl)pyridines and bis(arylaminosulfonylmethyl-azolyl)pyridines were synthesized from the synthetic intermediates methyl arylsulfonylacetic acid hydrazide and methyl arylaminosulfonylacetic acid hydrazide adopting a green methodology-ultrasonication. All the synthesized compounds were resulted in higher yield and in shorter reaction times. The spectral parameters such as IR, ¹H NMR, ¹³C NMR, mass and microanalyzes were used to determine the structures of all the synthesized compounds and were assayed for antioxidant activity. The bis(arylaminosulfonylmethylazolyl)pyridines showed higher radical scavenging activity than the bis(arylsulfonylmethylazolyl)pyridines. Besides, unsubstituted, and methyl substituted compounds exhibited greater activity. Among all the tested compounds 8b and 11b were identified as potential antioxidants.     

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 of Pyrimidine,Dihydropyrimidinone, and Dihydroimidazole Derivatives under Free Solvent Conditions and Their Antibacterial Evaluation

The biologically active compounds of pyrimidine, dihydropyrimidinone, and dihydroimidazole have been synthesized in excellent yield under free solvent conditions. The antibacterial evaluation of the products showed a high inhibitory effect. Reaction of 2‐guanidinobenzothiazole with several active methylene compounds has revealed formation of the corresponding pyrimidine, dihydropyrimidinone, and dihydroimidazole derivatives under free solvent conditions in very good yield. All compounds have been characterized on the basis of IR, ¹H NMR, ¹³C NMR, mass spectrometry, and X‐ray.     

Synthesis of new 1,2,3-triazole linked benzimidazolidinone: Single crystal X-ray structure,biological activities evaluation and molecular docking studies

A novel series of 1,2,3-triazole-benzimidazolidinone hybrid derivatives were designed and synthesized via click reaction, between various aryl azide and a terminal alkyne bearing a benzimidazolidinone moiety. All newly synthesized compounds, were efficiently characterized using ¹H NMR, ¹³C NMR and HRMS. Furthermore, the structure of one precursor 5b was supported by single crystal X-ray diffraction. All synthesized derivatives have been evaluated for their antimicrobial and anti-inflammatory activities. Biological activity tests exhibited that the target structures demonstrate that compounds 5a, 5b and 5f have a high antibacterial activity especially derivative 5b. Besides, the in vitro antifungal results revealed that the strongest inhibition recorded to compound 5b in comparison to other products against A. brasiliensis, A. fumigatus and C. albicans. Biological activity evaluation indicated that the synthesized compounds possess moderate anti-inflammatory effects. The most effective compound in terms of efficacy and potency was 5a. Molecular docking simulation was used to investigate the most active compounds' probable binding mechanisms in order to provide a plausible explanation for their biological activity.     

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.     

Synthesis and in vitro antioxidant evaluation of new bis(α-aminoalkyl)phosphinic acid derivatives

Diamines were added to arylaldehydes in ethanol, which resulted in corresponding diimines. Novel bis-1-aminophosphinic acid compounds were synthesized through the interaction of diimines and hypophosphorous acid. The new compounds were characterized by elemental analyses, FT-IR and ¹H, ¹³C and ³¹P NMR techniques. The in vitro antioxidant activity of the newly synthesized compounds were measured and found to exhibit significantly higher antioxidant activity than the standard.     

Design,synthesis, and characterization of some new benzimidazole derivatives and biological evaluation

A new series of benzimidazole derivatives ( 1-15 ) containing 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole, and thiazolidinon rings have been synthesized. All new synthesized benzimidazole compounds were confirmed by ¹H NMR, ¹³C NMR spectra, and LC-MS, and they were examined for their antioxidant and antimicrobial activities. Compounds 7 and 1 showed the highest and the lowest antioxidant activities, respectively. The lowest minimum inhibition concentration value found in compound 5 against Enterobacter aerogenes.     

Novel pyrimidine and its triazole fused derivatives: Synthesis and investigation of antioxidant and anti-inflammatory activity

In the present study, we have carried out the synthesis of novel dihydropyrimidinecarbonitrile (1a–c), its dimethylated adduct (2a–c), and hydrazine derivative (3a–c) of 2a–c and its triazole fused derivatives (4a–c, 5a–c and 6a–c). The structure of newly synthesized compounds was confirmed by IR, ¹H NMR, mass spectral data and elemental analysis. Further the novel derivatives were investigated for their in vitro antioxidant and anti-inflammatory activity. The results revealed that some of the tested compounds showed potent antioxidant and anti-inflammatory activity. The mass spectral pattern of 6a has been investigated in order to elucidate the structure.