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 and Antimicrobial Evaluation of Some New 4,5′‐Bisthiazoles

Thiazole and bisthiazole derivatives represent a prevalent scaffold in the antimicrobial drug discovery. Therefore, we have decided to synthesize some new series of 4,5′‐bisthiazoles. A total of 17 compounds were synthesized, their structural elucidation being based on elemental analysis (C,H,N,S) and spectroscopic data (MS and ¹H NMR). Their in vitro antimicrobial activities were assessed against several Gram‐positive and Gram‐negative bacteria strains and also against one fungal strain (Candida albicans) using the difusimetric method. Some of the compounds showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus and Bacillus cereus bacterial strains. All of the synthesized compounds showed moderate to very good antifungal activity against C. albicans.     

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 In Vitro Antibacterial Activity of Novel Steroidal (6R)‐Spiro‐1,3,4‐thiadiazoline Derivatives

Novel steroidal (6R)‐spiro‐1,3,4‐thiadiazoline derivatives were synthesized by the cyclization of steroidal thiosemicarbazones with acetic anhydride, screened in vitro against antibacterial activity using disc‐diffusion method and the minimum inhibitory concentration. 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 antibacterial activity. Among all the compounds, compound 7 and 8 were found better inhibitors of both types of bacteria (Gram‐positive and Gram‐negative) as compared to the respective drug amoxicillin. All the synthesized compounds were well characterized by spectroscopic methods such as IR, ¹H‐NMR, ¹³C‐NMR mass, and elemental analysis and their stereochemistry was also discussed.     

Facile Heterocyclic Synthesis and Antibacterial Activity of Substituted Isoxazol‐5(4H)‐ones

An efficient, simple, and green procedure for the synthesis of isoxazol‐5(4H)‐one derivatives are described here through a convenient one‐pot, three‐component reaction at room temperature. The title compounds are isolated in high to excellent yields and after short reaction times, and are characterized by various spectroscopic methods such as IR, ¹H NMR, and ¹³C NMR. The synthesized compounds 4a–c and 4e–i were tested for their in vitro activity against a panel of Gram‐positive and Gram‐negative bacteria, demonstrating their ability to inhibit microorganisms with a zone of inhibition ranging from 15 to 30 mm, minimum inhibitory concentration between 250 and 900 μg/mL, and minimum bacterial concentration between 700 and 1000 μg/mL.     

Synthesis and antibacterial activity of novel pyrano[2,3-d]pyrimidine-4-one–3-phenylisoxazole hybrids

A series of ethyl 2,7-dimethyl-4-oxo-5-phenyl-3-[(3-phenylisoxazol-5-yl)methyl]-3,5-dihydro-4H-pyrano[2,3-d]pyrimidine-6-carboxylates was synthesized and screened for antibacterial activity against Gram positive and Gram negative bacterial species. All new compounds were characterized by ¹H, ¹³C NMR, IR, and mass spectra. The results of the antibacterial study indicated that all compounds exhibited good to excellent antibacterial activity.

     

Efficient Synthesis of Novel 3‐Phenyl‐5‐thioxo‐3,4,5,6‐tetrahydroimidazo[4,5‐c]pyrazole‐2(1H)‐carbothioamide Derivatives Using a CeO2–MgO Catalyst and Evaluation of Antimicrobial Activity

Imidazo[4,5‐c ]pyrazole derivatives ( 3a–f , 4a–f , and 5a–f ) were efficiently synthesized by one‐pot three‐component reactions using CeO₂–MgO as the catalyst. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopic analyses. The in vitro antimicrobial activity of the synthesized compounds against various bacterial and fungal strains was screened. Compound 3b was highly active [minimum inhibitory concentration (MIC): 0.5 μg/mL] against Gram‐positive Staphylococcus aureus , and compounds 3b , 3f , 4d , and 4e were highly active (MIC: 0.5, 2, 2, and 0.5 μg/mL, respectively) against Gram‐negative Pseudomonas aeruginosa and Klebsiella pneumoniae , relative to standard ciprofloxacin in the antibacterial activity screening. Compounds 3b and 4f were highly active (MIC: 4 and 0.5 μg/mL, respectively) against Aspergillus fumigatus and Microsporum audouinii in the antifungal activity screening compared with the clotrimazole standard.     

Synthesis and Antimicrobial Evaluation of Novel Polyfused Heterocycles‐Based Quinolone

Syntheses of some new heterocyclic compounds incorporating quinolone moieties were achieved via reaction of 4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 1 ) or 3‐bromo‐4‐hydroxy‐7‐methoxyquinolin‐2(1H)‐one ( 2 ) with binucleophilic reagents. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H‐NMR and mass spectra). The newly synthesized compounds were screened for their antibacterial activity against Gram‐positive bacteria (Bacillus thuringiensis) and Gram‐negative bacteria (Escherichia coli). The results showed clearly that compounds 1 and 3 are the more potent antibacterial agents against E. coli, compounds 4 , 5 , 6 and 8 , 9 , 10 , 11 , 12 , 13 exhibited moderate activities against E. coli strain, and compounds 7 and 11 exhibited weak activities compared with Gentamicin as a well known standard drug.     

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.     

Novel 7‐Nitro‐1‐(Piperidin‐4‐yl)‐4,5‐Dihydro‐[1,2,4] Triazolo[4,3‐a]Quinoline‐Sulphonamide Derivatives as Antimicrobial Agents: Design,Synthesis, and Bio‐Activity

In attempt to search for more potent antimicrobial agents, a series of 7‐nitro‐1‐(piperidin‐4‐yl)‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐derived sulphonamides were synthesized. Their structures were established by elemental analyses, IR, and NMR (¹H and ¹³C) spectral data. The antibacterial activity of the obtained compounds was investigated against different Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Bacillus subtilis and Staphylococcus aureus) bacteria and antifungal activity against two fungal strains (Aspergillus niger and Aspergillus clavatus) using disk diffusion method at various concentrations (20, 40, 60, and 80 μg/mL). The study reveals that most of the title compounds showed significant antibacterial and fungal activity when compared with their respective standards streptomycin and griseofulvin.     

Microwave Assisted Green Synthesis of Pyrazole, 1, 2, 3‐ Triazole Based Novel Benzohydrazones and Their Antibacterial Activities

A series of novel pyrazole, triazole based benzohydrazones ( 7a‐l ) were synthesized via conventional and microwave methods in the presence of acetic acid catalyst. Microwave method provided green and economical approach towards the synthesis of novel Schiff bases ( 7a‐l ). Some intermediates and all the final compounds were characterized by NMR, mass, and elemental analysis. The compounds were screened for their in vitro antibacterial activity against Gram‐negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive bacteria (Staphylococcus aureus and Bacillus cereus). Compounds 7e and 7g showed good antibacterial activity.     

Synthesis and in vitro Antimicrobial Activity of Nalidixic Acid Hydrazones

A series of nalidixic acid‐based hydrazones have been synthesized and evaluated for their in vitro antimicrobial activity using the broth microdilution method against a panel of reference strains of microorganisms, including Gram‐positive bacteria, Gram‐negative bacteria, and fungi belonging to yeasts Candida spp. and molds Aspergillus spp., Penicillium spp., and Rhizopus spp. Nalidixic acid derivatives were obtained by condensation reaction of nalidixic acid hydrazide with substituted (hetero)aromatic aldehydes. All compounds have been characterized by ¹H NMR and ¹³C NMR spectra. The antimicrobial activity indicated that compound with indole substituent could be a promising lead for future development of active antifungal agents.     

Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide ( 1 ) with azomethine N‐oxide ( 2 ) have afforded novel isoxazolidine ( 3 ) in excellent yield. Their structures have been characterized from their IR, ¹H‐NMR, ¹³C‐NMR, ¹H,¹H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes ) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) using agar‐well diffusion assay. Some of the compounds ( 3a , 3k , 3n , and 3o ) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.     

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.     

Design,Regiospecific Green Synthesis,Chemical Computational Analysis,and Antimicrobial Evaluation of Novel Phthalazine Heterocycles

Phthalazines have received considerable attention for their wide antimicrobial activity. Regiospecific nucleophilic attack of 4‐benzylphthalazin‐1‐ol by the 1‐oxo rather than the aza group on different alkyl halides gave novel phthalazine heterocyclic derivatives. Moreover, a variety of nucleosides bonded to electron‐withdrawing groups were synthesized using 4‐benzylphthalazine‐1‐ol. The density functional theory has been used to investigate the electronic structure of the synthesized compounds. All of the synthesized derivatives showed remarkable activity when tested against Gram‐positive and Gram‐negative bacteria, Aspergillus niger, and Candida albicans. The reactivity of these nucleosides was expected to arise from their bonding with the lone pair of N‐atom of the macromolecules of bacteria. These bonding were expected to inhibit the enzyme by forming highly stable complex with lower highest occupied molecular orbital energy. The structures of these synthesized derivatives were established by Fourier transform infrared, ¹H‐NMR, and ¹³C‐NMR spectroscopic evidence.     

Synthesis and Antimicrobial Activity of Linked Heterocyclics Containing Pyrazole and Oxadiazoles

A new series of 3‐(arylaminomethyl)‐5‐(5‐methyl‐1‐phenyl‐1H‐4‐pyrazolyl)‐2,3‐dihydro‐1,3,4‐oxadiazole‐2‐thiones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j has been synthesized by the reaction of 5‐(5‐methyl‐1‐phenyl‐1H‐4‐pyrazolyl)‐1,3,4‐oxadiazol‐2‐ylhydrosulfide 5 with formaldehyde and corresponding anilines. The chemical structures of newly synthesized compounds were elucidated by IR, ¹H, ¹³C‐NMR, MS, and elemental analyses. The compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j were evaluated for their antibacterial activity against three representative Gram positive bacteria viz. Bacillus subtilis (MTCC 441), Bacillus sphaericus (MTCC 11) and Staphylococcus aureus (MTCC 96), and three Gram negative bacteria viz. Pseudomonas aeruginosa (MTCC 741), Klobsinella aerogenes (MTCC 39) and Chromobacterium violaceum. Among the screened 6b , 6d , 6i , and 6j in which oxadiazole moiety bearing 4‐fluoroanilinomethyl, 4‐chloroanilinomethyl, 2‐trifluoromethylanilinomethyl, and 2,5‐difluoroanilinomethyl groups, respectively, showed high activity against all the microorganisms used. In addition these compounds were also screened for their antifungal activity against four fungal organisms viz. Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996). Most of these new compounds showed appreciable activity against test fungi, and emerged as potential molecules for further development.     

Synthesis,Antimicrobial Studies,and Docking Simulations of New Bis(4,5‐dihydropyrazole) Derivatives

A novel series of bis(3‐thienyl‐4,5‐dihydropyrazoles) has been synthesized by the cyclization reactions of bischalcones with phenyl hydrazine in basic medium. The O‐alkylation reactions of chalcones with suitable 1,ω‐dibromoalkanes in the presence of anhydrous K₂CO₃, dry acetone, and Bu₄N⁺I⁻ as PTC lead to the formation of bischalcones in good yields. The chalcone required was obtained from the Claisen–Schmidt condensation reaction of 2‐acetylthiophene with 3‐hydroxybenzaldehyde. Structures of prepared compounds were elucidated from their IR, ¹H‐NMR, ¹³C‐NMR, and ESI‐MS spectral data. Newly synthesized compounds were screened for their antimicrobial potencies against Gram‐positive, Gram‐negative bacterial strains, and fungal strains using serial tube dilution method. Docking simulations have also been carried out to visualize the possible interaction of synthesized scaffold 2(a – g) and 3(a – g) at the active sites of Escherichia coli .     

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.     

Synthesis and in vitro Antimicrobial Activity of New Ethyl 2-(Ethoxyphosphono)-1-cyano-2-(substituted tetrazolo-[1,5-a]quinolin-4-yl)ethanoate Derivatives

A series of new ethyl 2‐(ethoxyphosphono)‐1‐cyano‐2‐(substituted tetrazolo[1,5‐a]quinolin‐4‐yl)ethanoate derivatives have been synthesized for the first time of tetrazolo[1,5‐a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, ³¹P NMR and mass spectral data elucidated the structures of the all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Gram‐positive Bacillus subtilis, Gram‐negative Escherichia coli and two fungi Candida albicans and Aspergillus niger in comparison with standard drugs. Significantly microbiological behavior of these newly synthesized derivatives possesses significant antibacterial and antifungal activity.     

Silica‐gel‐supported Phosphorus Pentoxide:a Simple and Efficient Solid‐supported Reagent for Esterification of Long‐ Chain Carboxylic Acids and Their Antimicrobial Screening

A silica-gel-supported heterogeneous phosphorus pentoxide reagent has been developed for the esterification of various long-chain carboxylic acids with aromatic alcohols. The reactions occurred under relatively mild conditions and afforded the desired products in good yields. All the compounds 3a—3x were screened for antibacterial and antifungal activity, which showed good activity against Gram positive and Gram negative bacteria and also good results against almost all fungal strains. The structures of the synthesized compounds were elucidated by IR, ¹H NMR, ¹³C NMR, mass spectroscopic techniques and elemental analysis.