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Background: The present study investigates the potential bioactivity of twelve experimentally designed C-2 quaternary indolinones against Providencia spp., a bacterial group of the Enterobacteriaceae family known to cause urinary tract infections. The study aims to provide insights into the bioactive properties of the investigated compounds and their potential use in developing novel treatments against Providencia spp. The experimental design of indolinones, combined with their unique chemical structure, makes them attractive candidates for further investigation. The results of this research may contribute to the development of novel therapeutic agents to combat Providencia spp. infections., Methods: The synthesized indolinones (moL1-moL12) are evaluated to identify any superior activity, particularly focusing on moL12, which possesses aza functionality. The antimicrobial activities of all twelve compounds are tested in triplicates against six different Gram-positive and Gram-negative organisms, including P. vermicola (P<0.05). Computational methods have been employed to assess the pharmacokinetic properties of the compounds., Results: Among the synthesized indolinones, moL12 exhibits superior activity compared to the other compounds with similar skeleton but different functional moieties. All six strains tested, including P. vermicola , demonstrated sensitivity to moL12. Computational studies support the pharmacokinetic properties of moL12, indicating acceptable absorption, distribution, metabolism, excretion, and toxicity characteristics., Conclusion: Utilizing the PPI approach, we have identified a promising target, FabD, in Gram-negative bacteria. Our analysis has shown that moL12 exhibits significant potential in binding with FabD, thereby, might inhibit cell wall formation, and display superior antimicrobial activity compared to other compounds. Consequently, moL12 may be a potential therapeutic agent that could be used to combat urinary tract infections caused by Providencia spp . The findings of this research hold significant promise for the development of new and effective treatments for bacterial infections., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Khataniar et al.)

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as 1 H-NMR, 13 C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01-SM-IMP-13 series have HOMO/LUMO gaps within 4.43-4.69 eV, whereas the compounds of the DA-01-DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24-4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities., Competing Interests: The authors declare no conflicts of interest.

Introduction: Antibiotic resistance is a global threat that has been increasing recently, especially with antibiotic overuse and misuse. The search for new antibiotics is becoming more and more indispensable., Methods: Design and synthesis of isatin derivatives as surrogates of SB-239629, a bacterial tyrosine-tRNA synthetases (TyrRS) inhibitor. The newly synthesized compounds were screened for their antimicrobial and antibiofilm activities. Docking studies were used to investigate potential binding modes of these compounds with TyrRS., Results and Discussion: Newly synthesized isatin-decorated thiazole derivatives (7b, 7d, and 14b) have shown potent antimicrobial activities against E. coli , a representative of gram-negative bacteria. Also, 7f showed the best activity against Methicillin Resistant Staphylococcus aureus (MRSA). In addition, 7h and 11f were found to have antifungal activities against Candida albicans equivalent to that of the reference Nystatin. All the new isatin derivatives with antimicrobial activities were found to exhibit strong biofilm distortion effects at half their minimum inhibitory concentrations (MIC). Moreover, thiazole derivatives 11a-f showed promising biofilm formation inhibition. Finally, molecular docking studies were used to investigate possible binding modes of target compounds with S. aureus and E. coli TyrRS., Conclusion: The novel isatin-decorated thiazole derivatives show strong antimicrobial and antifungal activities with potential action on TyrRS., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Kassab et al.)

A series of [4-amino-3-(4-chlorophenyl)-1H-pyrazol-5-yl](3,5-dimethyl-1H-pyrazol-1-yl)-methanone and 6-amino-3-(4-chlorophenyl)-5-methyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one have been synthesized from ethyl 4-amino-3-(4-chlorophenyl)-pyrazol-5-carboxylate. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)CNMR, Mass spectra and Elemental analysis. The compounds were evaluated for their in vitro antimicrobial and anticancer activity. Among the synthesized compounds, compounds 7a,b and 15 exhibited higher anticancer activity than the doxorubicin as reference drug. Most of the newly synthesized compounds have good to excellent antimicrobial activity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a-g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a-g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (-7.55 kcal/mol) with the active site of serine protease, better than compound 4c (-6.90 kcal/mol) as well as indole-based control compound 5 (-7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/ mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development. [ABSTRACT FROM AUTHOR]

In this context, we are interested to study the site-selectivity of the reaction of 3-amino-4-cyano-5-phenyl-1H-pyrrole-2-carboxylic acid amide 1 with different types of hydrazonoyl halides as well as the α-haloketones. The products of these reactions were confirmed from their spectral data and conformational studies to be pyrrolo[1,2-d][1,2,4]triazine and pyrrolo[1,2-a]pyrazine derivatives. We used docking studies to test the ability of the new synthesized pyrrolo[1,2-d][1,2,4]triazine and pyrrolo[1,2-a]pyrazine derivatives to dock and inhibit the microbes and COVID-19 proteins. The results of both docking studies revealed a strong fit of almost the tested derivatives into the active sites of peroxiredoxin 5 (Pdb: 2WFC; the overexpressed proteins in Candida albicans) and COVID-19 main protease (Pdb: 6LU7; severe acute respiratory syndrome coronavirus 2). Moreover, the antimicrobial activity of the products was investigated against two selected Fungi species and two G+ and two G− bacteria. The results of antimicrobial activity indicated that almost all derivatives showed no activity against fungi species, while all of them have moderate activity against bacteria strains (G+ and G− bacteria). [ABSTRACT FROM AUTHOR]

Introduction: Antibacterial drug resistance, brought on by the overuse of antibiotics, is one of the biggest threats to human health. It is crucial to consider cutting-edge strategies, such as herbal remedies, to control multidrug-resistant (MDR) bacteria. Methods: This study evaluated the phytochemical, antioxidant and antibacterial properties of the various Tinospora cordifolia extracts. Functionalization of the isolated active compound was done using gold (Au) and silver (Ag) nanoparticles (NPs). Further, to understand the interaction of the isolated class, Cordifolisides, with its target, various in-silico methods were used. Results and Discussion: The plant was reported from the Charaideo district of Assam, whose methanolic stem extract showed the maximum activity towards the nosocomial pathogen Pseudomonas aeruginosa. Consequently, the active compound was isolated and characterized as belonging to the class Cordifoliside using NMR. The AuNPs and AgNPs functionalized isolates showed enhanced antimicrobial activity against P. aeruginosa compared to the unfunctionalized isolate. The most reactive compound, Cordifoliside C was determined using Density Functional Theory (DFT) analysis, whose interactions with the TolB protein were studied using molecular docking methods, which revealed good binding interactions of Cordifoliside C with the TolB protein. Conclusion: This study offers enormous potential for drug design and might be used as a pipeline to address the urgent problem of multidrug-resistance in bacteria. [ABSTRACT FROM AUTHOR]

This study aims to synthesize a new series of furochromone derivatives, evaluate their antimicrobial properties, and improve the permeability of potent compounds to inhibit different types of bacteria and fungi. Hence, Substituted furo[3,2-g]chromene-6-carbonitrile (3a,b) readily form 7-amino-5-methyl-furo [3,2-g]chromene-6-carbonitrile (4a,b) via reduction using sodium borohydride in methanol. The same compounds of (4a,b) were used as starting materials for the synthesis of new furochromone derivatives such as furochromeno [2,3-d]pyrimidines, N- (6-cyano- 5-methyl-furochromene) acetamide, N-(6-cyano-5-methyl-furo chromene)-2-phenyl acetamide, N- (6-cyano-5-methyl-furochromene) formimidate, furochromeno[1,2,4]triazepin-5-amine, furochrom ene-6-carboxamide, furochromeno[1,2,4]triazolopyrimidines, and furochromeno[2,3-b]quinolin- 6-amine. The structures of the new compounds were determined using spectroscopy: Nuclear Magnetic Resonance (1H, 13C), Mass spectra, Infrared, and elemental analysis. Molecular docking studies were conducted to investigate the binding patterns of the prepared compounds against DNA-gyrase (PDB 1HNJ). The results displayed that compounds furochromenotriazolopyrimidine (20a,b), furochromenoquinolin-6-amine (21a,b), furochromenotriazepin-amine (9a,b), and furo- chromenopyrimidine-amine (19a,b) were excellent antimicrobials. [ABSTRACT FROM AUTHOR]

AbstractIn this context, we designed and synthesized a series of hydrazonal and their related indeno[1,2-b]pyridin-5-one derivatives to investigate their antibacterial and anti-biofilm properties. Several of the synthesized compounds exhibited significant efficacy against all microorganism species tested. Most of the compounds demonstrated favorable results when tested against Gram-positive bacteria. The derivatives 4a, 4f, 6c, and 6f exhibit the highest antimicrobial efficacy, as indicated by their minimum inhibitory concentration (MIC) values ranging from 4 to 512 μg/mL. We conducted additional investigations on 4a, 6c, and 6f for the purpose of examining their synergy using Checkerboard assay. Compound 6c demonstrated a synergistic impact against methicillin-sensitive Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa, while exhibiting moderate synergistic activity against methicillin-resistant Staphylococcus aureus (MRSA). In addition, the simultaneous use of gentamycin with compounds 4a and 6f demonstrates a synergistic impact in fighting against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. Three chosen compounds were evaluated for their antibiofilm efficacy. Application of 4a, 6c, and 6f effectively reduced the production of biofilms in MRSA, MSSA, and Pseudomonas aeruginosa, resulting in a significant decrease compared to the untreated samples. In addition, ADME and pharmacokinetic analyses were conducted for the three most potent derivatives, namely 4a, 6c, and 6f. Compounds 4a and 6c were subjected to docking in the LasR Quorum-Sensing Receptor, whereas compounds 6c and 6f were docked in the sortase enzyme. [ABSTRACT FROM AUTHOR]

• Five new 10-heterylazo-9-anthrone derivatives were synthesised and characterized. • The solvatochromic property of reported compounds is produced by the formation of H-bond complexes with solvents. • Based on molecular docking modelling, the pharmacokinetics and anticancer activity were evaluated for pancreatic cancer. • In vitro antibacterial activity was evaluated for the five anthrone derivatives with compound I described as the most active. • Compound III and IV presented a promising efficacy in combating pancreatic carcinoma. In this paper, a new series of five promising 10-heterylazo-anthracen-9(10 H)-one derivatives (I-V) was synthesized and screened for their antimicrobial activities. The chemical and tautomeric structures of the newly synthesized compounds were confirmed by FT-IR, UV, 1H- and 13C-NMR spectroscopy. Spectral investigation confirms the presence of tautomerism only for compounds I, III and IV. The electronic spectra and solvatochromic behavior of these compounds were studied and the solvated H-bond complexes formed in solution were examined. Solvatochromic behaviour of these compounds was studied by observing changes in the electronic spectra in mixture of solvents with different polarity. From the results it is evident that solvatochromic effect is produced by the formation of H-bond complexes. Results of antimicrobial screening demonstrated that these new derivatives had a respectable antibacterial activity and compound I emerged as the most active. In addition, molecular docking studies of all compounds and their isomers were performed to predict their binding patterns towards the active Rab20 site that is found regulated in the human pancreatic tumor. The results would suggest that these compounds could bind to Rab20 effectively which could result in important biochemical modification and probably affecting the growth and survival. Synthesis of new anthrone derivatives and their azo-hydrazone tautomeric forms. Image, graphical abstract [ABSTRACT FROM AUTHOR]