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 and Antimicrobial Screening of 2‐Aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of 2‐aryl‐5‐((2‐arylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives was synthesized by condensation of 2‐(2‐substituted thiazol‐4‐yl)acetohydrazide with aryl aldehydes followed by oxidative cyclocondensation using iodobenzene diacetate. The structure of synthesized compounds was characterized by IR, NMR, and mass analysis. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity. Some of the compounds showed moderate antimicrobial activity.     

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 and Antimicrobial Evaluations of Some Novel Mono‐, Bis‐, and Tris‐Nitro‐1,2,4‐Triazines

Substituted‐1,2,4‐triazines were conveniently synthesized in one pot by the cyclization of arylnitroformaldehyde hydrazone derivatives 1 and 5 with different primary amines in ~37% formaldehyde solution. The synthesized compounds were arranged into novel mono‐, bis‐, and tris‐nitro‐1,2,4‐triazine derivatives 2 , 3 , 4 , 6 , and 7 . The antibacterial and antifungal activity of the synthesized compounds were screened against bacterial strains Escherichia coli (as Gram − ve) and Staphylococcus aureus (as Gram + ve), and fungal strains Aspergillus flavus and Candida albicans . All the synthesized compounds exhibit various patterns of inhibitory activity on the two pathogenic bacterial strains. However, the same compounds showed no activity against the tested fungal strains.     

Synthesis and antimicrobial activity of 2<Emphasis Type="Italic">H</Emphasis>-pyrimido[2,1-<Emphasis Type="Italic">b</Emphasis>]benzothiazol-2-ones

4-Phenyl-2H-pyrimido[2,1-b]benzothiazol-2-ones have been synthesized in quantitative yields by the reaction of 2-aminobenzothiazoles with alkynoic acid. The antimicrobial activity of the synthesized compounds was tested against bacterial species, Bacillus coagulans, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. The synthesized compounds have shown significant activity against microorganisms which can be correlated with the fused heterocyclic systems.     

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,Characterization, and Antimicrobial Screening of 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole Derivatives

A series of novel 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole ( 8a‐p ) derivatives has been synthesized and screened for antibacterial activity against four pathogenic bacteria, Escherichia coli, Pseudomonas flurescence, Staphylococcus aureus, and Bacillus subtilis. Among them, compounds 8a and 8j exhibited excellent antibacterial activity with minimum inhibitory concentration range of 1.0 to 5.3 μg/mL and compounds 8m and 8p exhibited moderate to good antibacterial activity with minimum inhibitory concentration range of 16.9 to 29.7 μg/mL against all tested strains. All the synthesized compounds were screened for their in vitro antifungal activity against Cocinida candida. Most of the compounds reported moderate antifungal activity. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimicrobial agent.     

Synthesis and Evaluation of Some Novel 2‐Amino‐4‐Aryl Thiazoles for Antitubercular Activity

A series of novel 2‐amino‐4‐aryl thiazoles were synthesized from α‐chloroacetophenone and thiourea at room temperature using acetone as solvent. The structures of synthesized compounds were confirmed by spectral data. All the compounds were evaluated for antitubercular activity by macro broth dilution method against Mycobacterium Tuberculosis H37Rv as standard strain. The synthesized compound displays notable antitubercular activity.     

4‐Aryl‐4H‐Chromene‐3‐Carbonitrile Derivates: Synthesis and Preliminary Anti‐Breast Cancer Studies

A series of new 4‐aryl‐4H‐chromene‐3‐carbonitrile derivatives were obtained by one‐pot synthesis using substituted benzaldehydes, malononitrile, and substituted phenols. All the synthesized compounds ( 1a , 1b , 1c , 1d , 1e ) were screened in vitro for antioxidant and anticancer activities. Compounds 1c , 1d , 1e showed significant antioxidant activity in nitric oxide free radical scavenging method while compounds 1c and 1e showed significant activity in hydrogen peroxide free radical scavenging method. The other compounds showed significant to moderate activities in both the methods in comparison with ascorbic acid and butylated hydroxytoluene as standards. Compounds 1c , 1d , 1e exhibited good anticancer activity, using Michigan Cancer Foundation‐7 (MCF‐7) cell line, compared with those of other synthesized compounds.     

Asymmetric Synthesis and Antitumor Activity of Spiro‐Oxadiazole Derivatives from 1,4:3,6‐Dianhydro‐D‐fructose

A series of spiro‐oxadiazoles were synthesized from 1,4:3,6‐dianhydro‐D ‐fructose and hydrazides via a stereo‐ selective two‐step reaction sequence. The structures of newly synthesized compounds were established by spectral analysis. The absolute configuration of compound 2a was further confirmed by single crystal X‐ray analysis. All the synthesized compounds were screened for their in vitro antitumor activity, showing that these compounds have poor inhibitory activities against A549, MGC‐803 tumor cells.     

Synthesis and Evaluation of Antimicrobial Activity of Some New Hetaryl‐Azoles Derivatives Obtained from 2‐Aryl‐4‐methylthiazol‐5‐carbohydrazides and Isonicotinic Acid Hydrazide

A series of new 1,3,4‐oxadiazole/thiadiazole and 1,2,4‐triazole derivatives have been synthesized starting from 2‐aryl‐4‐methylthiazol‐5‐carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The synthesized compounds were screened for their antibacterial and antifungal activity, assessed as growth inhibition diameter. Some of them showed good antibacterial activity against gram positive Staphylococcus aureus, while the antibacterial activity against Listeria monocytogenes, Escherichia coli, and Salmonella typhymurium and antifungal activity against Candida albicans was modest. None of the tested compounds showed inhibitory activity against gram positive bacteria Enterococcus faecalis and Bacillus cereus and against gram negative bacteria Pseudomonas aeruginosa.     

Design and Synthesis of 2,5‐Disubstituted‐1,3,4‐Oxadiazole Hybrids Bearing Pyridine and 1,2,3‐Triazole Pharmacophores

A novel series of 2,5‐disubstituted‐1,3,4‐oxadiazoles decorated with two biodynamic moieties pyridine and 1,2,3‐triazole have been successfully synthesized in good yields under mild reaction conditions. The synthesized compounds are valuable for biological activity exploration since three biodynamic moieties are covalently linked together in a single molecular framework. All the synthesized compounds were fully characterized by their detailed spectral studies IR, ¹HNMR, ¹³C NMR and Mass.     

<em>N</em>-Substituted 5-Chloro-6-phenylpyridazin-3(2<em>H</em>)-ones: Synthesis, Insecticidal Activity Against <em>Plutella xylostella </em>(L.) and SAR Study

A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H)-one derivatives were synthesized based on our previous work; all compounds were characterized by spectral data and tested for in vitro insecticidal activity against Plutella xylostella. The results showed that the synthesized pyridazin-3(2H)-one compounds possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h which showed > 90% activity at 100 mg/L. The structure-activity relationships (SAR) for these compounds were also discussed.     

Novel Approach for Rapid and Efficient Synthesis of 2‐(3‐(4‐Aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one Derivatives and Screened Their Antimicrobial Activity

A series of compounds, viz. 2‐(3‐(4‐aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one 4 ( a – n ), have been synthesized by reaction of 3 ( a – n ) with thioglycolic acid in the presence of zinc chloride. Compounds 3 ( a – n ) have been synthesized by amination of formylated pyrazoles 2 ( A – B ), which were synthesized by formylation of 1 ( A – B ) by Vilsmeier–Haack reagent (POCl₃/DMF). Compounds 1 ( A – B ) were synthesized by condensation of hydrazide and substituted acetophenones under conventional method and microwave irradiation method. These compounds were identified on the basis of melting point range, Rf values, infrared, ¹H NMR, and mass spectral analysis. These compounds were evaluated for their in vitro antimicrobial activity, and their minimum inhibitory concentration was determined. Among them, compound 4b and compound 4l possess appreciable antimicrobial and antifungal activities. Antibacterial activity results showed that compounds containing electron‐withdrawing groups were more active than compounds containing electron‐releasing groups.     

Facile synthesis and biological evaluation of novel fluorine-containing <Emphasis Type="Italic">N</Emphasis>-nitro-<Emphasis Type="Italic">N</Emphasis>′-substituted phenylurea

Twenty-two novel N-nitro-N′-substituted phenyl-N-(2,6-dibromo-4-fluorophenyl)urea derivatives were designed and synthesized via a simple and convenient BTC ‘one-pot’ procedure using DMAP as the catalyst. The structures of all newly synthesized compounds were confirmed by IR, ¹H NMR, and elemental analysis, and a part has been identified by ¹³C NMR. The preliminary bioassay indicates that the target compounds possesses moderate herbicidal activity against Sorghum sudanense. However, some of the title compounds presented high plant growth regulating activity against rape.     

Synthesis and Evaluation of Some New (1,2,4) Triazolo(4,3‐a)Quinoxalin‐4(5H)‐one Derivatives as AMPA Receptor Antagonists

This study involves the synthesis and anticonvulsant evaluation of 1‐ethyl‐3‐hydrazinylquinoxaline‐2‐(1H)‐one ( 8 ), its chemical confirmations 9 and 10 and certain (1,2,4) triazolo(4,3‐a)quinoxalin‐4(5H)‐one compounds 11 , 12 , 13 , 13a , 13b , 13c , 13d , 13e , 13f , 14 , 15 , 16 . The structure of the synthesized compounds was confirmed chemically by elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and Mass). Docking studies were preformed to all of the synthesized compounds to predict, in a qualitative way, the anticonvulsant activity of the proposed compounds. There is a promising correlation between the results of molecular modeling and the anticonvulsant activity of the synthesized compounds. The highest fitting value was noticed for compounds 9 and 10 , which showed the highest anticonvulsant activity.     

Synthesis and Characterization of Some Heteroaromatic Derivatives of 3‐But‐2‐enoyl‐chromen‐2‐one and Their Potential as Anti‐inflammatory Agents

A novel series of chromen‐2‐ones containing pyrazole, isoxazole, oxazine, and thiazine substitutions have been synthesized by reacting 3‐[3‐(4‐chloro‐phenyl)‐acryloyl]‐chromen‐2‐one and 3‐[3‐(3‐methoxy‐phenyl)‐acryloyl]‐chromen‐2‐one with various cyclizing agents such as hydrazine, phenylhydrazine, urea, and thiourea. The structures of all the synthesized compounds were confirmed by the use of IR, ¹H‐NMR, mass spectroscopy, and elemental analysis data. All the newly synthesized compounds were evaluated for their anti‐inflammatory activity at a dose of 100 mg/kg body weight in carrageenan‐induced rat paw edema model. The entire series of the compounds exhibited moderate to good anti‐inflammatory activity, with the percentage inhibition of edema formation ranging from 39.99 to 63.15 against the reference drug ibuprofen (100 mg/kg) that showed 78.96% inhibition at the third hour. Compounds 3a , 3c , and 3d showed good inhibitory activity, whereas compounds 3b , 3e , 3f , and 3j showed moderate inhibitory activity at the third hour.     

Synthesis and Antimicrobial Activity of New Substituted 5‐(Pyridine‐3‐yl)‐1,3,4‐Thiadiazoles and Their Sugar Derivatives

New substituted 5‐(pyridine‐3‐yl)‐1,3,4‐thiadiazoles, their sugar hydrazones and acyclic C‐nucleoside analogs as well as the corresponding thioglycoside derivatives were synthesized. The synthesized compounds were tested for their antimicrobial activity against Escherichia coli, Bacillus subtilis, Staph aureus, Aspergillus niger, and Candida albicans The obtained results indicated that most of tested compounds exhibited moderate to high antimicrobial activity while few compounds were found to exhibit little or no activity against the tested microorganisms.     

Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.     

Synthesis and In Vitro Anticancer Activity of Novel 1,3,4‐Oxadiazole‐Linked 1,2,3‐Triazole/Isoxazole Hybrids

A series of new 1,3,4‐oxadiazole‐linked 1,2,3‐triazole/isoxazole derivatives were designed and synthesized. All the synthesized compounds were screened for in vitro anticancer activity against four human cancer cells: HeLa (cervical), MDA‐MB‐231 (breast), DU‐145 (prostate), and HEPG2 (liver). Among 17 compounds tested, 7a , 7c , and 7d showed potent activity toward four cell lines.