In this study, a new series of indole-5-carbaldehyde hydrazone derivative compounds were designed, synthesized, and their antimicrobial activities were determined by the microdilution method, and the in vitro cytotoxic effects on Beas-2b cell lines were investigated by MTT assay. When the activity results were examined, 5i12 showed promising activity against E. faecalis with MIC: 2 µg/mL compared to ampicillin, gentamicin, and vancomycin, although the antimicrobial activities of the indole derivatives were generally weaker than those of the standard drugs. Compounds showed no cytotoxic activity on the A549, MCF-7, and Beas-2b cell lines. Molecular docking studies were performed on 15 different proteins to understand the mechanism of 5i12's good antimicrobial action against E. faecalis, and it was concluded that the compounds interacted with FabH, not enough other protein structures. Molecular dynamics simulations were performed to investigate the protein–ligand stability of the most active compound against E. faecalis. The RMSD value of 5i12 varied between 0.02 and 0.16 nm during the MD simulation. The apoprotein peaked at 0.55 nm at the beginning of the simulation and stabilized below 0.5 nm. The theoretical ADME profiles of all compounds were calculated and found to comply with Lipinski and other limiting rules. In addition, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis for 5i12 were calculated using the 6-311 G (d,p) base set and DFT/B3LYP theory, and the results were visualized. Communicated by Ramaswamy H. Sarma
Bacterial infection today occupies a tremendous place in world health. The infection diseases were kept under control after the development of penicillin and further studies were performed on the development of new antibacterial agents. However, to date, bacterial resistance caused a big failure in the treatment of infectious disease and therefore, development of new antibacterial agents became important for human health. In the present study, we have designed, synthesized and elucidated the structures of new hydrazide-hydrazone compounds and their hybrid amide derivatives. The structures of the compounds were elucidated with spectroscopic methods and their purity were proven by TLC, HPLC-MS analysis. The antibacterial and antifungal activity studies of the novel molecules were investigated on different strains. Among the synthesized compounds, AA3a and AA4a appeared to show promising antibacterial activity. None of the compounds showed significant antifungal activity on Candida albicans. The drug likeness properties and boiled-egg plot analysis were performed for all of the compounds. The novel molecules showed no violation on Lipinski’s rule of five and all the molecules showed good gastrointestinal absorption properties in the in silico studies.
We previously synthesized a series of quinoline-2-carbaldehyde hydrazone derivatives and evaluated their antioxidant activities. In this study, the antimicrobial activities of these quinoline-2-carbaldehyde hydrazone derivatives were evaluated antimicrobial activity by the microdilution method, and there cytotoxic effect was investigated in MCF-7 and A549 cells by MTT assay. When the activity results were examined, although the antimicrobial activity of quinoline derivatives were equal or better than standard drugs in general, compound 4 (2 µg/mL) and 8 (1 µg/mL) against E. faecalis and 5 (8 µg/mL) against P. aeruginosa are the most effective derivatives of the series. Besides, disk diffusion test was applied to these three compounds, and significant zone formation was observed at 8 (7 mm) compared to vancomycin (9 mm). Compounds showed no antiproliferative in A549 and MCF-7 cell lines, and compound 4, 5, and 8, which showed the most effective antimicrobial activity, were examined in healthy cells (Beas-2b) and no effect on cell viability was found. To understand the mechanism of this action of these compounds against E. faecalis, molecular docking studies were performed on 15 different proteins, and it was concluded that the compounds interacted with FabH and not enough with other protein structures. The theoretical ADME profiles of compounds comply with Lipinski and other limiting rules. Also, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis of 8 were calculated with 6–311 G (d,p) base set and DFT/B3LYP theory, and the results were shown.
Objectives:The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds.Resistance to many antimicrobial agents requires the discovery of novel molecules.Materials and Methods: In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities.The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. Results:The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 μg/mL.The synthesized compounds showed good to moderate antimicrobial activity compared with the standards.Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 μg/mL against Staphylococcus aureus strain (ATCC 29213).Conclusion: Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities.Ethylparaben is currently used as an antibacterial agent and preservative for preparations.These studies are necessary since they detect the relationship between the substitutions and activity.
The discovery of new antimicrobial molecules is crucial for combating drug-resistant bacterial and fungal infections that pose a dangerous threat to human health. In the current research, we applied a molecular hybridization approach to synthesize original thiosemicarbazide-triazole derivatives starting from (S)-naproxen (7a-7k). After structural characterization using FT-IR, 1 H-NMR, 13 C-NMR, and HR-MS, the obtained compounds were screened for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Candida albicans ATCC 10231 and their isolates, as well. Although all compounds were found to be moderate antimicrobial agents, in general, their antibacterial activities were better than antifungal effects. Among the tested compounds, 7j carrying nitrophenyl group on the thiosemicarbazide functionality represented the best MIC value against S. aureus isolate. Finally, molecular docking studies were performed in the active pocket of S. aureus flavohemoglobin to rationalize the obtained biological data.
Abstract Hybrid structures containing multiple pharmacophore units with known activity have attracted attention due to their promising outcomes. In this study, several new hybrid structures containing benzimidazole and thiadiazole units were synthesized. The newly synthesized compounds were structurally analyzed using 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antimicrobial, in vitro anti-cancer, and antioxidant activities of all compounds were investigated. In vitro antimicrobial activities of the compounds were determined against Gram-positive (S. aureus ATCC 29213, E. faecalis ATCC 29212), Gram-negative (E. coli ATCC 25922, P. aeruginosa ATCC 27853) bacteria and fungi (C. albicans ATCC 10231) by using broth microdilution method. The compound 5g bearing 4-methoxyphenyl derivative showed the best activity with 32 μg/mL against S. aureus ATCC 29213 and P. aeruginosa ATCC 27853. The MTT test was used to determine the cytotoxicity of the produced compounds on the MCF-7 (human breast cancer) and L-929 (fibroblast) cell lines. FRAP method was used to determine the antioxidant properties of synthesized compounds. The Ferric Reducing Antioxidant Power of the compounds 5a, 5b, and 5c showed more antioxidant properties than vitamin E. The compound 5g stands out in the series in that it is not toxic on the healthy cell line and has promising antimicrobial activity.
One of the most serious threats to human health is the increasing prevalence of drug-resistant pathogens. The development of new antibiotics capable of combating drug resistance is critical. In various bacteria and plant species, 4-aminobenzoic acid (PABA) is produced and used as a substrate for folate generation. In this study, a new series of PABA analogs were synthesized and evaluated for their antimicrobial activity. Thirteen novel compounds were prepared by linking PABA hydrazide to sulfonate esters via a hydrazone bridge (4a–m). The structures of these compounds were characterized by 1H and 13C NMR and FT-IR spectroscopy as well as by LC-MS. Following structural characterization, all compounds were tested for their antimicrobial activity against Staphylococcus aureus (ATCC 29213), Enterococcus faecium (ATCC 19434), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 10231) strains. Four compounds were found to have moderate antimicrobial activity against the P. aeruginosa strain. These compounds, including 4e, 4f, 4g, and 4m, containing a hydrazide-hydrazone sulfonate functionality, showed the best MIC value of 64 μg/mL. In addition, synergistic effects of ascorbic acid, salicylic acid, and N-acetyl cysteine (NAC) with synthesized compounds were also investigated. It was observed that the combination of compounds 4f and 4g with NAC showed antipseudomonal activity with MIC values of 32 μg/mL and 16 μg/mL, respectively, against the P. aeuriginosa strain. The antimicrobial activity of 4f and 4g was enhanced by two folds in combination with NAC. Our findings in this study can be crucial for the development of new potent antimicrobial agents.
We study the fundamental, operational, and aftermarket characteristics of special purpose acquisition companies (SPACs) created in the U.S. during the years 2003-2008. We compare the characteristics of the 156 firms that chose to merge with SPACs to become a public company with the 794 firms that chose the traditional initial public offering (IPO) route. In addition, we analyze the changes in SPAC and IPO firms’ operational performance and stock market returns in the year following the floatation of new shares. Operational performance of SPAC firms is significantly inferior to their industry peers and to contemporaneous IPO firms. SPAC firms carry more debt, are smaller, invest less, and have lower growth opportunities than the firms that conduct a conventional IPO. While excess stock returns for both IPO and SPAC firms are negative, they are substantially more negative for SPAC firms.
