Synthesis, antimicrobial evaluation, and molecular docking studies of new tetrahydrocarbazole derivatives

Mohamed, Neama A.; El-Serwy, Walaa S.; El-Karim, Somaia S. Abd; Awad, Ghada E. A.; Elseginy, Samia A.

doi:10.1007/s11164-015-2090-6

Cited by 13 publications

(6 citation statements)

References 29 publications

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“…Similarly, hydrazide-hydrazones containing azomethine (-NHN=C) and thiosemicarbazide derivatives represent important classes of compounds for new antimicrobial drug development [37][38][39]. Molecular hybridization is a critical tool for discovery of new chemical entities and based on the aforementioned observation and in continuation of our previous studies in the antimicrobial field [40][41][42][43], the present study was focused on design and synthesis of two sets of novel benzimidazole compounds through combination of benzimidazole scaffold with different biologically active pharmacophores in a single molecular framework as shown in (Fig. 2).…”

Section: Introductionmentioning

confidence: 96%

Design, Synthesis and Molecular Docking of New Benzimidazole Derivatives of Potential Antimicrobial Activity as DNA Gyrase and Topoisomerase IV Inhibitors

et al. 2021

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A new series of benzimidazole derivatives 3a-3d, 4a-4c, 8a-8d, 9a,9b, 10a-10d and 11 was synthesized and evaluated as antimicrobial agents against various gram-positive, gram-negative bacteria and fungi using vibramycin and fluconazole as positive controls for the antibacterial and antifungal activities, respectively. The examined microbial strains showed variable sensitivities against the target compounds.The examined microbial strains showed variable sensitivities against the target compounds. The minimum inhibitory concentration (MIC) was determined for the compounds showed zone of inhibition ≥ 16 mm (4a, 4c, 8a, 10a). The latter derivatives were also examined as S. aureus DNA gyrase/topoisomerase IV inhibitors. The compounds 4a, and 8a represented the most promising activity for both enzymes in ATPase assay (IC50 4a 0.39, 0.52 and 8a 0.66, 0.28 µM respectively) as well as the safest profile against the human normal WI38 cells upon comparing with Ciprofloxacin and Novobiocin. Compounds 8a showed dual inhibitory effect against both targets DNA gyrase and topoisomerase IV in supercoiling and decatenation assay (IC50 0.443 and 1.15 µM respectively). Both compounds 4a and 8a can be considered as lead compounds for further structural modifications to obtain more potent DNA gyrase and topoisomerase inhibitors as antibacterial agents. Molecular docking study was performed for the most promising compounds to explore the pharmacophoric moieties that governed their binding with amino acid residues of DNA gyrase and topoisomerase IV using MOE software. The results revealed a binding mode and docking scores comparable to those of a reference ligand and consistent with their DNA gyrase and topoisomerase IV inhibition activity.

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Section: Introductionmentioning

confidence: 96%

Design, Synthesis and Molecular Docking of New Benzimidazole Derivatives of Potential Antimicrobial Activity as DNA Gyrase and Topoisomerase IV Inhibitors

et al. 2021

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“…It focused on the synthesis and antimicrobial activity of compounds produced by combining two biologically active compounds (NSAIDS and THCZ). THCZ and Carbazole ring scaffolds are present in some alkaloids [2], they have a variety of biological effects such as antiviral (3) , antitumor (4) , antibacterial (5,6) and broad-spectrum antifungal activity [7,8]. NSAIDs are considered as non-antibiotic drugs reported to display antibacterial activity [9], Some NSAIDs such as indomethacin and diclofenac have been shown to have synergistic effect with particular antimicrobial drugs [10].…”

Section: Introductionmentioning

confidence: 99%

Untitled

2022

J. Med. Chem. Sci.

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New 6-chloro-1,2,3,4-tetrahydrocarbazole compounds were prepared from the reaction of cyclohexanone with 4-chlorophenylhydrazine. The synthesis of heterocyclic compounds was carried out through the reaction of cyclohexanone with 4-chlorophenylhydrazine, then the produced compound was treated with two NSAIDs (indomethacin, diclofenac) by amide bond formation to form N-substituted THCZ by NSAIDs. The characterization of prepared compounds was identified using the 1 H, 13 C NMR and FT-IR spectroscopies. The antimicrobial activity of the synthesized compounds was tested in vitro to discover a good activity as antifungal and moderate as antibacterial, which was confirmed by the docking study of the compounds.

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“…Bacterial diseases have become one of the most serious global dangers in recent decades. The rise of pathogenic bacteria resistant to antibacterial medications in both community- and hospital-acquired diseases poses a severe danger to global health because currently existing drugs will no longer be effective Gram-negative bacilli Escherichia coli and Salmonella enterica (subtype typhi), which can cause deadly diarrheal disorders, and Pseudomonas aeruginosa, which colonizes in immune compromised patients as those with cystic fibrosis, cancer, or AIDS are among the bacteria deemed a priority for new treatments . Furthermore, despite the availability of effective antibiotics, the majority of clinical isolates of Gram-positive Staphylococcus aureus are resistant to a variety of medications.…”

Section: Introductionmentioning

confidence: 99%

Pharmacophore-Based Virtual Screening and Molecular Dynamics Simulation for Identification of a Novel DNA Gyrase B Inhibitor with Benzoxazine Acetamide Scaffold

Elseginy

Anwar

2021

ACS Omega

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DNA gyrase B is one of the enzyme targets for antimicrobial drug development, and its absence in mammals makes it a suitable target for the creation of safe antibacterial drugs. We identified six novel hits as DNA gyrase B inhibitors in the present study by employing 3D-pharmacophore structure-based virtual screening. The lead compounds complied with drug-likeness rules and lacked toxicity. Compound 4 (ZINC32858011) showed the highest inhibitory activity with an IC 50 value of 6.3 ± 0.1 μM against the DNA gyrase enzyme. In contrast, the positive controls ciprofloxacin and novobiocin used in enzyme inhibition assay had IC 50 values of 14.4 ± 0.2 and 12.4 ± 0.2 μM, respectively. The molecular docking of the six hits demonstrated that compounds 1, 2, 4, and 6 had suitable fitting modes inside the binding pocket. Molecular dynamics simulations were carried out for the six hits and the rmsd, rmsf, radius of gyration, and solvent accessible surface area parameters obtained from 100 ns molecular dynamics simulations for the six compounds complexed with a DNA gyrase B protein indicated that compound 4 (ZINC32858011) formed the most stable complex with DNA gyrase B. The binding free energy calculation with the MM-PBSA method suggested that the van der Waals interaction, followed by electrostatic force, played a significant role in the binding. Per-residue free binding energy decomposition showed that Ile78 contributed the most for the binding energy followed by Asn46, Asp49, Glu50, Asp73, Ile78, Pro79, Ala86, Ile90, Val120, Thr165, and Val167.

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Synthesis, antimicrobial evaluation, and molecular docking studies of new tetrahydrocarbazole derivatives

Cited by 13 publications

References 29 publications

Design, Synthesis and Molecular Docking of New Benzimidazole Derivatives of Potential Antimicrobial Activity as DNA Gyrase and Topoisomerase IV Inhibitors

Design, Synthesis and Molecular Docking of New Benzimidazole Derivatives of Potential Antimicrobial Activity as DNA Gyrase and Topoisomerase IV Inhibitors

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Pharmacophore-Based Virtual Screening and Molecular Dynamics Simulation for Identification of a Novel DNA Gyrase B Inhibitor with Benzoxazine Acetamide Scaffold

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