Abstract
Secnidazole was linked with ciprofloxacin as mutual prodrugs to get antibiotics with broader spectrum of activity, improved physicochemical properties and given by single dose to improve patient’s compliance. Furthermore, they provide structural modifications to overcome bacterial adaptation. The structures of the synthesized compounds were confirmed using FT-IR, mass spectrometry, elemental microanalysis (CHNO) and some physiochemical properties. This modification was led to an increase in Log P values for Mutual I (Log P 1.114) and Mutual II (Log P 1.97) compared with its values for Secnidazole (Log P -0.373) and ciprofloxacin (Log P -0.832). The solubility of prodrugs had been determined in different media, Mutual II showed 144-fold increase in aqueous solubility compared to ciprofloxacin. Taste evaluation by panel method showed palatable taste in prodrugs compared to the parent drugs. The synthesized compounds were screened for their antimicrobial activity against different bacterial strains which are, Staphylococcus aureus, Pseudomonas aeruginosa, E. coli and Klebsiella pneumonia. The prodrugs have revealed excellent antibacterial activities compared with the parent compounds. Chemical hydrolysis study at pH (1.2 and 7.4) has indicated that these compounds may pass unhydrolyzed through the stomach and produce enough stability to be absorbed from the intestine as indicated by t1/2 values.
Highlights
In a clinical practice the treatment for anaerobic infections aims to treat a complex ecosystem of multiple bacterial species with an antibiotics regimen that provide effective activity against both anaerobic and facultative bacteria [1]
Ciprofloxacin, a fluoroquinolone drug, is highly effective against many clinically vital pathogens which are responsible for variety of infections comprising gastrointestinal infections, urinary tract infections (UTI), sexually transmitted diseases (STD), respiratory tract infections (RTI) and are clinically useful against infections of skin, prostatitis, bones and penicillin resistant sexually transmitted disease [3,4]
The reaction sequences for the synthesis of the Mutual I was accomplished and outlined in scheme 1, that include activation the carboxyl group of ciprofloxacin by thionyl chloride to get ciprofloxacin acid chloride (Ia) that attacks secnidazole in a basic condition to give Mutual I
Summary
In a clinical practice the treatment for anaerobic infections aims to treat a complex ecosystem of multiple bacterial species with an antibiotics regimen that provide effective activity against both anaerobic and facultative bacteria [1]. Current therapeutic interventions available for anaerobic infection relies on combining two or more antibiotics for providing adequate antimicrobial coverage for both components. In combination, these antibiotics should be synergistic or at least not antagonistic in activity against microorganisms [2]. The effectiveness and broad spectrum activity of fluoroquinolone have made this class most heavily consumed antibacterial agent worldwide Due to their uncontrolled use, bacteria have evolved resistance against large groups of these compounds [6]. Ciprofloxacin is classified as class 4 compound according to the Biopharmaceutical Classification System (BCS), meaning that it possesses poor solubility as well as poor gastrointestinal permeability. This is due to the strong intermolecular bonds (van der Waals and hydrogen bonding interactions) that allow the molecules to pack densely in a solid-state structure [8]
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