Application of salting-out thin layer chromatography in computational prediction of minimum inhibitory concentration and blood-brain barrier penetration of some selected fluoroquinolones

Rageh, Azza H.; Atia, Noha N.; Abdel‐Rahman, Hamdy M.

doi:10.1016/j.jpba.2018.07.010

Cited by 10 publications

(2 citation statements)

References 40 publications

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“…Various investigations have employed different techniques, including thin-layer chromatography, RP-HPLC, and even the use of an immobilized artificial membrane (IAM) column. Drawing from our prior expertise in estimating the lipophilicity of FQs derivatives, we have opted for a protocol centered around the chromatographic hydrophobicity indices (CHI) as introduced by Valko and his colleagues 13 – 19 .…”

Section: Resultsmentioning

confidence: 99%

“…Several reports indicated that the chromatographic approach can be considered an efficient tool for lipophilicity assessment of FQs antibiotics and their derivatives. Some reports are based on thin-layer chromatography 13 , 14 while others applied RP-HPLC 15 considering also immobilized artificial membrane (IAM) column 16 . Summarizing our previous experience in lipophilicity estimation of FQs derivatives 17 , 18 , we have chosen a protocol based on the chromatographic hydrophobicity indices (CHI) proposed by Valko and co-workers 19 .…”

Section: Discussionmentioning

confidence: 99%

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Menthol- and thymol-based ciprofloxacin derivatives against Mycobacterium tuberculosis: in vitro activity, lipophilicity, and computational studies

Szulczyk,

Woziński,

Koliński

et al. 2023

Sci Rep

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In this work, we investigated the antitubercular properties of Ciprofloxacin derivatives conjugated with menthol and thymol moieties. For the sixteen derivatives, we established minimal inhibitory concentrations (MIC) using isolates of Mycobacterium tuberculosis that were resistant or susceptible to other antibiotics. For the most potent compound 1‐cyclopropyl‐6‐fluoro‐7‐{4‐[6‐((1R,2S,5R)‐2‐isopropyl‐5‐methylcyclohexyloxy)‐6‐oxohexyl]piperazin‐1‐yl}‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid (6), we determined fractional inhibitory concentration index (FICI) values to confirm antibacterial susceptibility and synergistic effects with other reference drugs. In addition, chromatographic studies of all the derivatives demonstrated a significant three to four-fold increase in lipophilicity and affinity to phospholipids compared to Ciprofloxacin. Finally, we conducted structure-based studies of the investigated compounds using molecular docking and taking into account protein target mutations associated with fluoroquinolone resistance. In summary, our findings indicate that the investigated compounds possess tuberculostatic properties, with some showing similar or even better activity against resistant strains compared to reference drugs. Increased lipophilicity and affinity to phospholipids of the new derivatives can offer several advantages for new drug candidates, beyond just improved cell membrane penetration. However, further studies are needed to fully understand their safety, efficacy, and mechanism of action.

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Section: Resultsmentioning

confidence: 99%