Facile Synthesis, Characterization and Antimicrobial Activity of 2-Alkanamino Benzimidazole Derivatives

Benzimidazole derivatives are known to represent a class of medicinally important compounds which are extensively used in drug design and catalysis. A series of 2-substituted benzimidazole derivatives 10a-i was herein synthesized from the reaction of o-phenylenediamine with some amino acids using ameliorable pathway. The chemical structures of the synthesized compounds were con rmed by IR, UV, 1H-NMR, 13C-NMR, Mass spectral and analytical data. The compounds were investigated for their antimicrobial activity alongside gentamicin clinical standard. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents. The most active compound was 1H-benzo[d]imidazol-2-yl)methanamine, 10a

Comparative Study of the Antibacterial Activity of N, N-Diethylamido Substituted p-Toluenesulfonamides to their α-Toluenesulfonamide Counterparts

Reaction of p-toluenesulfonyl chloride with amino acids gave sulfonamides p-T1a-k which upon amidation afforded p-T2a-k. Similarly, treatment involving α-toluenesulfonyl chloride and amino acids afforded the sulfonamides α-T1a-k. These two classes of sulfonamides were synthetically modified at their COOH end position to achieve N,N-diethylamido substituted p-toluenesulfonamides p-T2a-k and α-toluenesulfonamides α-T2a-k, respectively. The chemical structures of the compounds were validated with IR, Mass spectra, NMR as well as elemental analytical data. Both classes of compounds were screened against Escherichia coli and Staphylococcus aureus and their activity were compared. It was remarkable to note that the α-toluene sulfonamides α-T2a-k were more active than their p-toluenesulfonamide counterparts p-T2a-k. Compound 1-(benzylsulfonyl)-N,Ndiethylpyrrolidine-2-carboxamide α-T2a was the most potent antibacterial compound on S. aureus with MIC value of 3.12 μg mLG1 while N,N-Diethyl-3- phenyl-2-(phenylmethylsulfonamide) propanamide α-T2j emerged as the best antibacterial motif against E. coli with MIC value of 12.5 μg mLG1. Hence, these compounds especially the α-toluenesulfonamide core structural templates are good candidates for further study for future drug discovery

Evaluation of the performance of Ortho T. cruzi ELISA test system for the detection of antibodies to Trypanosoma cruzi

The serologic diagnosis of chronic Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is challenging and lacks a gold-standard assay. To overcome the problem, CDC uses an algorithm that uses two tests on different platforms and applies a third test as a tiebreaker. The Ortho T. cruzi ELISA Test System from Ortho Diagnostics was cleared by FDA for clinical diagnosis usage. We evaluated this test against the CDC algorithm for chronic Chagas disease. We tested several sets of serum specimens: 104 specimens tested positive for T. cruzi specific antibody and 283 (including 30 specimens positive for antibody to Leishmania spp.) tested negative based on the current CDC chronic T. cruzi infection diagnostic testing algorithm. Concordance of the Ortho T. cruzi ELISA Test System with the CDC algorithm result was 90% (95% CI 87 to 93%) overall and 92% (95% CI 89 to 95%) when excluding Leishmania spp. antibody positive specimens. The cross-reactivity of the Ortho T. cruzi ELISA Test System was 37% to Leishmania spp. serologically positive specimens, 1% to specimens from patients diagnosed with other parasitic infections, and 0% against specimens from a US noninfected population. In conclusion, the Ortho T. cruzi ELISA Test System compares well against the CDC diagnostic algorithm for chronic Chagas disease. The availability of this FDA-cleared assay will improve the chronic Chagas disease diagnosis. © 2022 American Society for Microbiology. All rights reserved

Comparative Study of the Antibacterial Activity of N, N-Diethylamido Substituted p-Toluenesulfonamides to their α-Toluenesulfonamide Counterparts

Reaction of p-toluenesulfonyl chloride with amino acids gave sulfonamides p-T1a-k which upon amidation afforded p-T2a-k. Similarly, treatment involving α-toluenesulfonyl chloride and amino acids afforded the sulfonamides α-T1a-k. These two classes of sulfonamides were synthetically modified at their COOH end position to achieve N,N-diethylamido substituted p-toluenesulfonamides p-T2a-k and α-toluenesulfonamides α-T2a-k, respectively. The chemical structures of the compounds were validated with IR, Mass spectra, NMR as well as elemental analytical data. Both classes of compounds were screened against Escherichia coli and Staphylococcus aureus and their activity were compared. It was remarkable to note that the α-toluene sulfonamides α-T2a-k were more active than their p-toluenesulfonamide counterparts p-T2a-k. Compound 1-(benzylsulfonyl)-N,Ndiethylpyrrolidine- 2-carboxamide α-T2a was the most potent antibacterial compound on S. aureus with MIC value of 3.12 μg mLG1 while N,N-Diethyl-3- phenyl-2-(phenylmethylsulfonamide) propanamide α-T2j emerged as the best antibacterial motif against E. coli with MIC value of 12.5 μg mLG1. Hence, these compounds especially the α-toluenesulfonamide core structural templates are good candidates for further study for future drug discovery

Microwave-assisted synthesis and antibacterial propensity of N0-s-benzylidene-2-propylquinoline- 4-carbohydrazide and N0-((s-1H-pyrrol- 2-yl)methylene)-2-propylquinoline- 4-carbohydrazide motifs

Microwave-assisted approach was utilized as green approach to access a series of 2-pro pylquinoline-4-carbohydrazide hydrazone derivatives 10a-j of aromatic and heteroaromatic aldehydes in highly encouraging yields. It involved four steps reaction which was initiated with ring opening reaction of isatin in a basified environment and subsequent cross-coupling with pentan-2-one to produce compound 7. Esterification of 7 in acid medium led to the formation of compound 8 which was reacted with hydrazine hydrate to access 9 which upon microwave-assisted condensed with aromatic and heteroaromatic aldehydes furnished the targeted compounds 10a-j. The structures of 10aj were confirmed by physico-chemical, elemental analyses and spectroscopic characterization which include UV, FT-IR, 1H and 13C NMR as well as DEPT-135. The targeted compounds 10a-j, alongside with gentamicin clinical standard, were investigated for their antibacterial efficacies using agar diffusion method. 2-Propyl-N0-(pyridine-3-ylmethylene) quinoline-4-carbohydrazide 10j emerged a

Structure-based design of functionalized 2-substituted and 1,2- disubstituted benzimidazole derivatives and their in vitro antibacterial efficacy

The aim of this present study was to synthesize 2-substituted and 1,2-disubstituted benzimidazole derivatives to investigate their antibacterial diversity for possible future drug design. The structurebased design of precursors 2-(1H-benzimidazol-2-yl)aniline 1, 2-(3,5-dinitro phenyl)-1Hbenzimidazole 3 and 2-benzyl-1H-benzimidazole 5 were achieved by the condensation reaction of ophenylenediamine with anthranilic acid, 3,5-dinitrophenylbenzoic acid, and phenylacetic acid, respectively. The precursors 1, 3 and 5, upon reaction with six different electrophile-releasing agents, furnished the corresponding 2-substituted benzimidazole, 2a-f and 1,2-disubstituted benzimidazole derivatives 4a-f and 6a-f, respectively. The structural identity of the targeted compounds was authenticated by elemental analytical data and spectral information from FT-IR, UV, 1H, and 13C NMR. The outcome of the findings from the in vitro screening unveiled 2-benzyl-1-(phenylsulfonyl)-1H-benzimidazole 6b as the most active derivative with lowest MIC value of 15.63 mg/m

Microwave assisted synthesis, characterization and investigation of antibacterial activity of 3-(5- (substituted-phenyl)-4,5-dihydro-1H-pyrazol-3- yl)-2H-chromen-2-one derivatives

A variety of 3-(5-(substituted-phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one derivatives 3a–j were synthesized through microwave assisted thermal annulation of corresponding a,b-unsaturated ketones (chalcones) 2a–j via hydrazinolysis. Chalcones 2a–j were prepared from 3-acetyl-coumarin 1 which was previously accessed by Pechmann condensation reaction of salicylaldehyde. The series of pyrazoline-based coumarin motifs 3a–j synthesized, were structurally confirmed by analytical and spectral data. They were then evaluated for their antimicrobial activities using agar diffusion method. The result showed that microwave assisted method (MAM) for the reaction was remarkably successful and gave the targeted products 3a–j in higher yields at shorter reaction times compared to conventional synthetic method (CSM). The results showed that these skeletal frameworks exhibited marked potency as antibacterial agents. The most active antibacterial agent was 3-(5-(4- (diethylamino) phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-2H-chromen-2-one 3j with MIC and MBC values of 3.92 ± 0.22 mg/mL and 7.82 ± 0.43 mg/mL respectively.The World Academy of Sciences (TWAS)https://www.tandfonline.com/loi/tabs20am2020Chemistr

Facile Synthesis, Characterization and <i>in vitro</i> Antibacterial Efficacy of Functionalized 2-Substituted Benzimidazole Motifs

A series of functionalized 2-substituted benzimidazole motifs was designed and successfully synthesized via thermal cyclization of 1,2-diaminobenzene on COOH end of L- leucine to achieve benzimidazole derivatives 6 as the essential precursor. The coupling of the precursor 6 with benzaldehyde derivatives a-h, ketone series i-k, and aryl sulfonyl chlorides l-n led to the formation of the targeted 2-substituted benzimidazole motifs 7a-n in improved yields. The targeted benzimidazole motifs were structurally authenticated through their spectral data and microanalytical parameters. The targeted final moieties were investigated for potential antimicrobial activity using the agar diffusion method with gentamicin as the clinical standard. All the compounds had a broad spectrum of activity with compound 7k having the highest remarkable activity with MIC of 0.98 ± 0.02 µg/mL and MBC value of 3.91 ± 0.10 µg/mL. These findings suggest that compound 7k containing camphor might be a good candidate for the design of new antimicrobial small-molecule drugs

Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs

Introduction: Quinazolin-4(3H)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3H)-one motifs as potential antimicrobial drug candidates.Methods: The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3H)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3H)-one motifs 3a–l, and with thiophene-2-carbaldehyde to afford 3 m. The purified targeted products 3a–m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-one motifs 3a–m were screened for both in silico and in vitro antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively.Results and discussion: Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein–ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3H)-one 3 m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95 μg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90 μg/mL) against Candida albicans, Aspergillus niger, and Rhizopus nigricans

A diverse view of science to catalyse change

Valuing diversity leads to scientific excellence, the progress of science and, most importantly, it is simply the right thing to do. We must value diversity not only in words, but also in actions