Four push–pull fluorescent thiophene–furan analogues (ATVTCF) 5a-d were synthesized, and their chemical structures were secured by the IR, 1H-NMR, 13C NMR, and mass spectral performances. The synthesized ATVTCF analogues 5a-d were assessed for their absorbance and fluorescence characteristics across different solvents, highlighting the considerable effect of solvent polarity on Stokes shifts, which was applied to be marked by the definite category of aryl and thiophene-vinyl connection in conjunction with the p-phenyl donor part. Additionally, the presence of phenyl, anisyl, n-butyl, and dimethylamino groups was originated to impact the maximum absorbance. Meanwhile, the antibacterial evaluation of synthesized fluorophores ATVTCF 5a-d toward Gram (+ ve) and Gram (− ve) bacterial pathogens was performed, through the measurement of (IZD) and (MIC) values in contrast to amoxicillin (reference). Among the targeting analogues, ATVTCF-5a demonstrated the most significant antibacterial effect, particularly against K. pneumoniae, with an IZD = 23 mm and an MIC = 21.14 µg/mL. ATVTCF-5b and ATVTCF-5c showed moderate antibacterial activity, whereas ATVTCF-5d exhibited the least effectiveness. On the other hand, the DNA gyrase inhibition activity of synthesized ATVTCF analogues was measured as IC50 values (µM) to determine the potency of each analogue. Among the tested analogues, ATVTCF-5c demonstrated the highest DNA gyrase inhibition (IC50 = 5.47 µM), while ATVTCF-5d showed the weakest activity (IC50 = 9.03 µM). Comparatively, novobiocin (reference compound) exhibited the strongest inhibition (IC50 = 4.24 µM). These results indicate that the ATVTCF analogues, particularly ATVTCF-5c and ATVTCF-5b, are promising candidates for DNA gyrase inhibition, though further optimization may be required to enhance their efficacy. Moreover, the molecular docking examination was pragmatic on the ATVTCF analogues to assess their bindings inside the pockets of DNA gyrase, and their corresponding affinities were matched with the results of the DNA gyrase inhibition. Among the studied analogues, ATVTCF-5b revealed the good score of binding (− 7.6109 kcal/mol), likened to the novobiocin (reference) drug. Furthermore, the pharmacokinetic properties of four ATVTCF analogues using the SwissADME program showed that all analogues exhibited moderate solubility and satisfactory bioavailability values, and ATVTCF 5a showed the highest GI absorption and inhibition of multiple CYP450 isoforms.

Synthesis, Photophysical Properties, Antibacterial Activity, DNA Gyrase Inhibition, and Molecular Docking Studies of New Thiophene–Furan Push–Pull Fluorophores

期刊论文
发表日期：

2025年3月22日

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Samar Y. Al nami,
Aisha Hossan

摘要

Four push–pull fluorescent thiophene–furan analogues (ATVTCF) 5a-d were synthesized, and their chemical structures were secured by the IR, ¹H-NMR, ¹³C NMR, and mass spectral performances. The synthesized ATVTCF analogues 5a-d were assessed for their absorbance and fluorescence characteristics across different solvents, highlighting the considerable effect of solvent polarity on Stokes shifts, which was applied to be marked by the definite category of aryl and thiophene-vinyl connection in conjunction with the p-phenyl donor part. Additionally, the presence of phenyl, anisyl, n-butyl, and dimethylamino groups was originated to impact the maximum absorbance. Meanwhile, the antibacterial evaluation of synthesized fluorophores ATVTCF 5a-d toward Gram (+ ve) and Gram (− ve) bacterial pathogens was performed, through the measurement of (IZD) and (MIC) values in contrast to amoxicillin (reference). Among the targeting analogues, ATVTCF-5a demonstrated the most significant antibacterial effect, particularly against K. pneumoniae, with an IZD = 23 mm and an MIC = 21.14 µg/mL. ATVTCF-5b and ATVTCF-5c showed moderate antibacterial activity, whereas ATVTCF-5d exhibited the least effectiveness. On the other hand, the DNA gyrase inhibition activity of synthesized ATVTCF analogues was measured as IC₅₀ values (µM) to determine the potency of each analogue. Among the tested analogues, ATVTCF-5c demonstrated the highest DNA gyrase inhibition (IC₅₀ = 5.47 µM), while ATVTCF-5d showed the weakest activity (IC₅₀ = 9.03 µM). Comparatively, novobiocin (reference compound) exhibited the strongest inhibition (IC₅₀ = 4.24 µM). These results indicate that the ATVTCF analogues, particularly ATVTCF-5c and ATVTCF-5b, are promising candidates for DNA gyrase inhibition, though further optimization may be required to enhance their efficacy. Moreover, the molecular docking examination was pragmatic on the ATVTCF analogues to assess their bindings inside the pockets of DNA gyrase, and their corresponding affinities were matched with the results of the DNA gyrase inhibition. Among the studied analogues, ATVTCF-5b revealed the good score of binding (− 7.6109 kcal/mol), likened to the novobiocin (reference) drug. Furthermore, the pharmacokinetic properties of four ATVTCF analogues using the SwissADME program showed that all analogues exhibited moderate solubility and satisfactory bioavailability values, and ATVTCF 5a showed the highest GI absorption and inhibition of multiple CYP450 isoforms.