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.     

ZnO Nanocatalyst Mediated Convergent Synthesis of Highly Substituted Imidazole and Imidazole‐derived Bi‐heterocyclic Scaffolds as Potential Antibacterial Agents

A new series of novel highly substituted imidazole and imidazole bi‐heterocycles have been synthesized via atom economic, one‐pot condensation reaction using benzil, substituted benzaldehydes, various amine scaffolds, and ammonium acetate using ZnO nanoparticles as effective catalyst. Simple operation, cheap catalyst, good to excellent yield, etc, are some of the advantages of this protocol. The characterization of the synthesized imidazole analogues was performed by Fourier transform infrared, nuclear magnetic resonance (¹H and ¹³C), mass analysis, and elemental analysis. The structures were unequivocally confirmed by single‐crystal X‐ray diffraction analysis. Synthesized compounds were tested for antibacterial activities by resazurin reduction assay. All compounds tested showed significant activity against bacteria. Among the 24 compounds tested, compounds 1c , 1i , 2c , 2g , and 3a proved to be more active against the bacterial strain tested.     

A “One Pot,” Environmentally Friendly,Multicomponent Synthesis of 2‐Amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines and Their Antimicrobial Activity

A series of multifunctional 2‐amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines ( 4a , 4b , 4c , 4d , 4e , 4f ) was synthesized by multicomponent reaction of 3‐formylindole ( 1 ), cyanoethylacetate ( 2 ), and guanidine hydrochloride ( 3 ) with NaOH by using green chemical techniques, viz. microwave irradiation and grindstone technology. The same reactants when refluxed in ethanol also gave titled compounds ( 4a , 4b , 4c , 4d , 4e , 4f ). Compared with conventional procedure, the reaction can be carried out under milder conditions, requiring a shorter reaction time and giving higher yields following the green chemistry methodology. All the synthesized compounds have been characterized on the basis of elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and mass). All synthesized compounds were also evaluated for their antimicrobial activity against nine pathogenic bacteria, antifungal activity against Rhizopus stolonifer, Aspergillus flavus, and Fusarium oxysporum and antibacterial activity against Escherichia coli and Pseudomonas aeruginosa at different concentrations. Most of the compounds showed mild to moderate activity.     

Synthesis and in vitro Study of Novel Methylenebis(phenyl- 1,5-benzothiazepine)s and Methylenebis(benzofuryl-1,5- benzothiazepine)s as Antimicrobial Agents

A series of methylenebis(phenyl-1,5-benzothiazepine)s 4 and methylenebis(benzofuryl-1,5-benzothiazepine)s 5 were prepared by the reaction of methylene-bis-chalcones 3 with 2-aminothiophenol for 4 and followed by the condensation with chloroacetone for 5. The structures of the synthesized compounds have been confirmed by their IR, 1H NMR, 13C NMR, MS and elemental analyses. All the synthesized compounds were tested for their antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. To elucidate the essential structural requirements for the antimicrobial activity, the preliminary structure-activity relationship has been described. Among the compounds tested, the dimeric compounds 4f, 4g, 5f and 5g were found to be most active against Bacillus subtilis, Bacillus sphaericus, Staphylococcus aureus, Klebsiella aerogenes and Chromobacterium violaceum. Similarly these dimeric compounds showed potent antifungal activity against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes. It is interesting to note that the dimeric compounds with substituents of heterocyclic ring at the 4th position of benzothiazepine system displayed notable antibacterial activity equal to that of streptomycin and penicillin. Further, the activity of all the dimeric compounds was compared with that of their monomeric compounds, and it is interesting to note that almost all the dimeric compounds showed enhanced activity than their monomeric compounds.     

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.     

An Efficient Access to Pyrimidine‐based Polyfunctional Heterocycles with Anticipated Antibacterial Activity

6‐Amino‐2‐thioxotetrahydropyrimidine‐5‐carbonitrile derivative 2 was synthesized in a good yield via refluxing a mixture of arylidene 1 and thiourea in a highly basic sodium ethoxide solution. Subsequently, the synthesized pyrimidine‐2‐thione derivative 2 was allowed to interact with diversified nucleophiles and electrophiles under various reaction conditions in order to have a feasible access to further new and assorted fused heterocycles. Finally, the biological activity of the newly synthesized fused pyrimidines was screened in vitro against four different Gram‐positive and Gram‐negative bacterial strains. All the developed heterocycles were adequately characterized utilizing ¹H‐NMR, ¹³C‐NMR, Fourier transform infrared, elemental analysis, and electrospray ionization–mass spectrum and tested for their antibacterial activity.     

Organoiodine(III) Mediated Synthesis of Novel Symmetrical Bis([1,2,4]triazolo)[3,4‐a:4′,3′‐c]phthalazines as Antibacterial and Antifungal Agents

A series of new symmetrical 3,6‐bis(aryl)bis([1,2,4]triazolo)[3,4‐a:4′,3′‐c]phthalazines 9a‐l has been conveniently synthesized by oxidative cyclization of 1,4‐bis(substituted benzalhydrazino)phthalazines 8a‐l promoted by iodobenzene diacetate under mild conditions (12 examples, up to 93% yield). All the 12 compounds were tested in vitro for their antibacterial activity against two Gram‐positive bacteria, namely, Staphylococcus aureus, Bacillus subtilis and two Gram‐negative bacteria, namely, Escherichia coli and Pseudomonas aeruginosa. All the synthesized compounds were also tested for their antifungal action against two fungi, Aspergillus niger and Aspergillus flavus.     

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,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 of New Fused Thienopyrimidines Derivatives as Anti‐inflammatory Agents

5‐Amino‐2‐(p‐tolylamino)‐4‐phenylthieno[2,3‐d]pyrimidine‐6‐carbonitrile 9 , which was synthesized by an innovative method, was used as a versatile precursor for synthesizing pyrimido‐thienopyrimidine, triazolopyrimidothienopyrimidine, and pyrimidothienotriazine compounds. Thus, reaction of aminothienopyrimidinecarbonitrile 9 with chloroacetylchloride in dioxane afforded the chloroacetylaminocarbonitrile derivative 10 , which underwent nucleophilic substitution reactions with various primary and secondary amines gave the corresponding N‐alkyl‐(aryl)amino acetamides 11a,b . On the other hand, the reaction of aminocarbonitrile 9 with triethyl orthoformate followed by cyclization with hydrazine yielded an aminoiminopyrimidine derivative 13 . The latter was used as versatile precursor for synthesis of new heterocyclic compounds. The structures of all the new compounds have been established on the basis of their analytical and spectral data (IR, ¹H NMR, ¹³C NMR, and MS). Some of the synthesized compounds were evaluated in vitro for their anti‐inflammatory activity. All the tested compounds exhibited remarkable anti‐inflammatory activity.     

Synthesis and Antimicrobial Evaluation of New Monocyclic β‐Lactams

A simple, practical, and efficient approach to synthesize new series of 2‐(3‐(2,4‐dichlorophenoxy)‐2‐(4‐(dimethylamino)phenyl)‐4‐oxoazetidin‐1‐ylamino)‐N‐arylacetamide by Staudinger [2 + 2] cycloaddition reaction. The titled compounds were evaluated for their antibacterial and antifungal activity against eight microorganisms. All the newly synthesized compounds are characterized by IR, ¹H‐NMR, and mass spectroscopic data.     

Novel Steroidal (6R)‐Spiro‐1,3,4‐thiadiazoline Derivatives as Anti‐bacterial Agents

Novel steroidal (6R)‐spiro‐1,3,4‐thiadiazoline derivatives have been synthesized by the cyclization of steroidal thiosemicarbazones. Thiosemicarbazones have been synthesized by the reaction of steroidal ketones with thiosemicarbazide. All the compounds have been characterized by IR, ¹H NMR, mass and elemental analyses. The antibacterial activities of these compounds have been first tested in vitro by the disk diffusion assay against two Gram‐positive and two Gram‐negative bacteria, and then the minimum inhibitory concentration (MIC) values have been determined with the reference of standard drug amoxicillin. The results showed that steroidal thiadiazoline derivatives exhibited better antibacterial activity than the steroidal thiosemicarbazone derivatives. Chloro and acetoxy substituents on the 3β‐position of the steroidal thiadiazoline ring increased the anti‐bacterial activity. Among all the compounds, compounds 7 and 8 were found better inhibitors as compared to the respective drug amoxicillin.     

DBU Promoted Facile Synthesis of New Thieno[2,3‐b]pyridine/quinoline Derivatives and Their Antimicrobial Evaluation

Several new thieno[2,3‐b]pyridine and thieno[2,3‐b]quinoline derivatives are synthesized in an efficient manner catalyzed by DBU as a base. Simple workup procedure, good yields, and mild reaction conditions are the salient features of this method. All the synthesized compounds are screened for antimicrobial activity against several organisms.     

Synthesis,Characterization, and Molecular Docking of Novel bis‐thiazolyl Thienothiophene Derivatives as Promising Cytotoxic Antitumor Drug

A novel, facile reaction for the synthesis of series of bis‐thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and bis‐2‐bromoacetylthieno[2,3‐b ]thiophene derivatives in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, and ¹H and ¹³C NMR) and elemental analyses. Fifteen compounds of the synthesized compounds were evaluated for their anticancer activity against human liver hepatocellular carcinoma cell line (HepG2). All compounds showed anticancer activity but differs in potency comparable with the reference drug Cisplatin. Moreover, molecular docking study using MOE software predicted the best binding mode between the most active compound 5o into the active site of human heat‐shock protein 90. The computational studies are confirming the results in biological activity.     

Synthesis,Dissociation Constants,and Antimicrobial Activity of Novel 2,3‐Disubstituted‐1,3‐thiazolidin‐4‐one Derivatives

In this article, a new series of 2,3‐disubstituted‐1,3‐thiazolidin‐4‐one derivatives have been designed, synthesized, and evaluated as antimicrobial agents. New compounds were prepared by the cyclization reaction of N‐substituted carboxylic acid hydrazide derivatives with mercaptoacetic acid. The structures of the obtained compounds were confirmed by means of IR, ¹H NMR, and ¹³C NMR spectra. The dissociation constants were determined using spectrophotometric method. All synthesized compounds were tested for their in vitro antibacterial and antifungal activities using the broth microdilution method.     

Synthesis,Crystal Structure,and Biological Activity of Novel Anthranilic Diamide Insecticide Containing Propargyl Ether Group

In search of environmentally benign insecticides with high activity, low toxicity, and low residue, a series of novel anthranilic diamide containing propargyl ether were designed and synthesized. All compounds were characterized by ¹H NMR spectroscopy, high‐resolution mass spectrometry, or elemental analysis. The single crystal structure of 18g was determined by X‐ray diffraction. The insecticidal activities against Lepidoptera pests of the new compounds were evaluated. Their insecticidal activities against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentration.     

Cyanoacetamide Intermediate in Heterocyclic Synthesis: Synthesis and Biological Evaluation of Hitherto New Dioxoisoindoline Heterocyclic Derivatives

Innovative poly‐substituted heterocyclic rings incorporating dioxoisoindoline ( 2 – 25 ) were synthesized through the reaction of dioxoisoindoline derivative 2 as starting compound with various types of reagents. All compounds were characterized by appropriate means of (¹H‐NMR, ¹³C‐NMR, IR, and mass). The prepared compounds were evaluated as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and Candida albicans microorganisms. The tested compounds exhibited low to moderate antibacterial activities and promising results as antifungal agents.     

Synthesis and Antimicrobial Activity of Novel Azolopyrimidines and Pyrido‐Triazolo‐Pyrimidinones Incorporating Pyrazole Moiety

A new series of azolopyrimidine derivatives incorporating pyrazole moiety were synthesized by reaction of 1‐(pyrazol‐3‐yl)‐2‐propenone with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The mechanism of formation of the products was also discussed, and the structure assigned was elucidated based on both elemental and spectral analyses data. In addition, 7‐(pyrazolyl)‐2‐thioxo‐5‐phenyl‐1,3‐dihydropyrido[2,3‐d ]pyrimidin‐4‐one was used as starting material for preparation of a new series of pyridotriazolopyrimidines via its reaction with a variety of hydrazonoyl chlorides in dioxane using triethylamines as catalyst. The assigned structure for these products was also proved via elemental analysis and spectroscopic techniques (IR, ¹H NMR, and Mass). Moreover, the antimicrobial activity of some selected examples of the new products was evaluated, and the results obtained revealed high activity of compound 20a against the Gram positive bacteria Staphylococcus aureus and the Gram negative bacteria Klebsiella pneumonie . All the tested compounds have no antifungal activity.     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

Synthesis of chloro,fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative ( 11 ) was novel. The structures of the synthesized compounds were elucidated by means of ¹H, ¹³C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC₅₀ values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.