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Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinol...
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Herein we report the synthesis of different derivatives of (fluoro)quinolones norfloxacin, ciprofloxacin and pipemidic acid, by incorporating (benzoylamino)methyl on the free nitrogen of the pyperazinyl moiety. The compounds were structurally characterized by 1D and 2D NMR, FTIR and high-resolution mass spectroscopy. In addition, their physicochemi...
INTRODUCTION. Enterobactericeae are associated with many types of infections including abscesses, pneumonia, meningitis, septicaemia, and intestinal, urinary and wound infections. Fluoroquinolones (FQs) represent the drug of choice for the treatment of a wide range of human infectious diseases caused by enterobacteriaceae. This study aimed at compa...
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... DNA cleavage and ligation processes are made possible by the TOPRIM domain of the subunit GyrB, which is where the divalent ions bind. Topoisomerase IV's ParC subunits are in control of the cleavage and re-ligation reaction as well as DNA binding [61]. The binding and hydrolysis of ATP are carried out by the ParE subunits. ...
Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.
Graphical abstract
Several Quinolone derivatives based on the SAR approach as potent antimicrobial agents which combat antimicrobial resistance.
... 10,13 Quinolones represent a class of broad-spectrum antibiotics that stand out as suitable ligands, due to their good oral absorption, excellent bioavailability, and great potential for structural modification. 33 Quinolone derivatives and their metal complexes have been extensively investigated for their potential antioxidant, antiviral, anti-HIV, antimalarial, and anticancer activities among others. 34,35 Although organotin(IV)-quinolone compounds have great potential, only a few studies on organotin(IV)-fluoroquinolone compounds have been reported so far. ...
Three newly synthesized triphenyltin(IV) compounds, Ph3SnL1 (L1− = 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoato), Ph3SnL2 (L2− = 2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato), and Ph3SnL3 (L3− = 2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato), were characterized by elemental microanalysis, FT-IR spectroscopy and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. A single X-ray diffraction study indicates that compounds Ph3SnL1 and Ph3SnL2 exhibit a 1D zig-zag chain polymeric structure, which in the case of Ph3SnL2 is additionally stabilized by π-interactions. In addition, the synthesized compounds were further examined using density functional theory and natural bond orbital analysis. The compounds have
been evaluated for their in vitro anticancer activity against three human cell lines: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three murine cell lines: 4T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in
the nanomolar range, indicating that these compounds possess better anticancer activity than cisplatin. The study of the effect of the newly developed drug Ph3SnL1 showed its plasticity in achieving an antitumor effect in vitro, which depends on the specificity of the phenotype and the redox status of the malignant cell line and ranges from the initiation of apoptotic cell death to the induction of differentiation to a more mature cell form. In the syngeneic model of murine melanoma, Ph3SnL1 showed the potential to mreduce the tumor volume similar to cisplatin, but in a well-tolerated form and with low systemic toxicity, representing a significant advantage over the conventional drug.
... The LC-MS analysis suggested that both influent and effluent samples contained a very large number of transformation products (Table 3). From the above discussion, it can be said that the majority of the transformation products (TPs) could be metal-ligand complex compounds, since the pharmaceutical products are strong ligands that can combine with metal ions in varying proportions, such as 1:1, 1:2, 1:3, 1:4, and mixed ligand complexes too [34]. These complexes are highly stable and toxic to aquatic biota, and due to their inertness, they can manage to bypass removal mechanisms [34,35]. ...
... From the above discussion, it can be said that the majority of the transformation products (TPs) could be metal-ligand complex compounds, since the pharmaceutical products are strong ligands that can combine with metal ions in varying proportions, such as 1:1, 1:2, 1:3, 1:4, and mixed ligand complexes too [34]. These complexes are highly stable and toxic to aquatic biota, and due to their inertness, they can manage to bypass removal mechanisms [34,35]. ...
... The presence of a strong ligand, especially chelating agents like EDTA, citrate, antibiotics, etc., inhibits adsorption on adsorbents because of strong complex formation with the metal ions or by competing with the surface for available adsorption sites. Complex formation occurs at a higher pH for the elimination of protons (H + ) formed during the reaction process [34,35]. In the WWTP, the influent was heated at a pH above 12 with sodium hydroxide (NaOH), which provided favourable conditions to form metal complexes with pharmaceutical products. ...
Pharmaceutical industries produce a huge volume of emerging pollutants (EPs) that pose a threat to the aqueous environment. Biological processes have shown their inefficacy in treating many pharmaceutical products. The study assessed physicochemical parameters, EPs, heavy metals in pharmaceutical industrial wastewater, and the removal efficiency (RE) of an aerobic biological treatment plant. The study also assessed the contamination levels and risk using several indices, such as the Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI), heavy metal pollution index (HPI), heavy metal evaluation index (HEI), and risk quotients index (RQs). The study found that the treated water quality was poor, having antibiotics, nonsteroidal anti-inflammatory drugs, and others, along with several transformation products (TPs) and heavy metals, which were unsafe for consumption with high environmental risk. The analysis results showed that the RE for TSS, BOD5, COD, TDS, and EC were found to be 91.80%, 86.81%, 72.29%, 72.20%, and 65.60%, respectively, where the values of BOD5, COD, NO3⁻, and PO4³⁻ in the effluent were still higher than the permissible limits of the ECR (2023). However, the RE for heavy metals was in the order of Cu (84.62%) > Fe (65.04%) > Mn (63.3%) > Zn (60.58%) > Cd (53.85%) > Ni (54.12%) > Pb (42.42%) > Cr (38%), where Cr and Cd concentrations were still higher than the permissible limit of DoE (2019). The Pearson correlation and PCA suggested that EC, TDS, TSS, DO, BOD5, and COD were the most correlating and contributing variables. This study argued that metal-ligand behaviors mainly affect the removal efficiency of the treatment plant by lowering the removal rate of heavy metals and pharmaceutical products.
... However, a wide variety of enzymes and protein cofactors comprise hundreds of inorganic complexes and metals that are vital to the proper functioning of the biological system and our bodies. Because of their biological importance and their crucial role in maintaining vital biological processes, chemists are drawn to the synthesis and application of coordination compounds and organometallics (Efthimiadou et al., 2008;Chohan et al., 2010;Uivarosi, 2013). ...
The research investigates the synthesis of tosylated 4-aminopyridine complexed with cobalt(II), iron(II), and nickel(II) and its used as antibacterial agents. The purity of the ligand and its complexes was determined using melting point and thin-layer chromatography techniques. The chemical properties were assessed by the utilisation of Ultraviolet-Visible Spectroscopy (UV-VIS), Infrared (IR), Molar Conductivity, Electrospray Ionisation Mass Spectrometry (ESI-MS), and Nuclear Magnetic Resonance (NMR) techniques. The free imine nitrogen in the ligands vibrated at a higher frequency than the complexes' coordinated imine. This suggests the transfer of lone pair electrons from the free azomethine nitrogen to the metal ions. A variety of microorganisms was used to determine the antimicrobial potential of both ligand and their complexies. The findings revealed that the ligand had no effect on bacterial or fungal strains, whereas, the complexes were sensitivity on some microbes. The bioactivity of monotosylated 4-aminopyridine was greatly enhanced by its complexes. Among the clinical pathogens, S. cerevisiae is most affected by the iron(II) complex.
... As mentioned above, ligands also have an impact on anticancer activity, and the literature suggests that a ligand must provide a relatively stable ligand-tin bond and its slow hydrolytic decomposition [21]. Quinolones, antibiotics with good oral absorption, safety and excellent availability, are among the most desirable heterocycle skeletons in drug research [22,23]. They have a privileged structure for variety modifications, and many quinolone derivatives are used in medicinal chemistry due to their biological activity, such as antibacterial, antitubercular, antimalarial, anti-HIV, anti-HCV, anticancer, etc. [22,24,25]. ...
A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.
... The interaction between multivalent cations and (fluoro)quinolones is well-documented in the gastrointestinal tract, leading to clinically significant reductions in their efficacy during human therapy (e.g., Uivarosi, 2013;Walden et al., 2021). Based on this phenomenon, which supports our findings, an increased Ca content may enhance the likelihood of chelation with DFX, primarily at the carbonyl and carboxyl groups (positions 3 and 4), leading to the formation of inactive compounds (Uivarosi, 2013). ...
... The interaction between multivalent cations and (fluoro)quinolones is well-documented in the gastrointestinal tract, leading to clinically significant reductions in their efficacy during human therapy (e.g., Uivarosi, 2013;Walden et al., 2021). Based on this phenomenon, which supports our findings, an increased Ca content may enhance the likelihood of chelation with DFX, primarily at the carbonyl and carboxyl groups (positions 3 and 4), leading to the formation of inactive compounds (Uivarosi, 2013). These positions also serve as binding sites for DNA and bacterial enzymes (DNA-gyrase and topoisomerase IV), which are receptors for DFX functions (as well as all (fluoro)quinolone antibiotics) (Cuprys et al., 2018). ...
... 9,10 In addition, many drugs such as antibiotics possess better pharmaceutical properties when they are in the form of metal transition complexes. [11][12][13] From this perspective, the synthesis and characterization of new metal complexes and the evaluation of their antibacterial activities have been considered by the global community as part of the solution to overcome AMR. 14,15 Transition metal complexes with 1,10-phenanthroline ligands are of much interest since they display a wide variety of applications in organometallic chemistry, catalysis, electrochemistry, ring-opening metathesis polymerization and biochemistry. ...
A novel iron(iii) complex (CH3)2NH2[Fe(phen)Cl4] (1) (phen = 1,10-phenanthroline) was synthesized, its structure was fully characterized using different techniques, and its in vitro antibacterial activity against various antibiotic-resistant Gram-positive and Gram-negative bacteria was evaluated. The structure of 1 is made up of mononuclear [Fe(phen)Cl4]⁻ anions and dimethylammonium cations (CH3)2NH2⁺. Iron(iii) is hexacoordinated to two nitrogen atoms of chelating phenanthroline and four chlorides forming a distorted octahedral environment around the metal atom. Complex 1 crystallizes in a triclinic system with the P1̄ space group. 3D Hirshfeld surfaces and 2D fingerprint plots show that H⋯Cl interactions are the major contributors in maintaining the total surface. IR and UV-visible spectra indicated the coordination of 1,10-phenanthroline to iron (iii) metal. Thermal stability experiments revealed that 1 is stable up to 428 K. Magnetic susceptibility measurements indicated a paramagnetic behavior at high temperatures. In vitro antibacterial activity was explored against two Gram-positive bacteria, Staphylococcus aureus CECT 86 and Listeria monocytogenes CECT 4031, and two Gram-negative bacteria, Escherichia coli CECT 99 and Klebsiella pneumoniae CECT 143T, using the disc diffusion method. Complex 1 clearly showed good activity against these bacteria and is a potential candidate for treating bacterial infections and promoting further development in their treatment.
... Tetracyclines form metal complexes with magnesium and can act as chelators of this cation. The formation of complexes between tetracycline and zinc is also important for the action of this antibiotic on the cells of the human body [21] . ...
The action of antibacterial antibiotics on bacteria but also on the cells of the human body is dependent on many factors. An important place is the interactions with magnesium and zinc. The aim of this narrative review is to highlight the complexity of interactions between these two cations and some antibacterial antibiotics. The review presents pharmacokinetic, pharmacodynamic interactions and the influence of magnesium and zinc on some adverse effects of antibiotics. The influences of some antibiotics on plasma concentrations of magnesium and zinc are also discussed. The interactions take place before the contact of the antibiotic with the pathogenic bacteria, during the action on bacteria but also after this action. Some adverse effects of antibiotics are produced by their direct action on human cells and plasma and tissue concentrations of magnesium and zinc are important for reducing these effects. These two biometals play multiple and complex roles in the human body. Some antibiotics such as aminoglycosides and polymyxins greatly increase the renal excretion of magnesium and significantly decrease the plasma concentration of this cation. Zinc increases the bacterial sensitivity to the action of beta-lactams. The polymerization of vancomycin dimers increases the antibacterial activity and it is dependent of zinc. Zinc oxide nanoparticles have a significant antibiofilm action. On the other hand, magnesium and zinc salts greatly reduce the digestive absorption of many antibiotics and decrease their bioavailability. Regarding adverse effects, there are situations were magnesium and zinc can reduce some of these effects. A low magnesium level aggravates the cartilage damage produced by quinolones. This cation reduces nephrotoxicity of Aminoglycosides and vancomycin and hepatotoxicity of some antituberculosis drugs. Determination of zinc and magnesium concentration is strictly necessary for patients receiving antibiotics and in the case of abnormal levels, correction must be made immediately.
... It should be noted that the presence of metal ions in biological fluids could have a significant effect on the therapeutic action of such organic compounds [32]. Such metal complexes were produced also from reactions between NA and several metal complexes [33][34][35][36][37][38][39]. ...
... This, in general, is owed to the presence of heteroatom functional groups, such as hydroxyl, thioether, carboxylic acid, and carbonyl, that might be involved in coordination with metals. The antibiotic-metal complexes (AMCs) are studied to possess different behavior for photolysis, adsorption, toxicity, bioavailability, and solubitily, compared to parent antibiotics (Graouer-Bacart et al., 2015;Guerra et al., 2016;Serna-Galvis et al., 2021;Sultana et al., 2013;Uivarosi, 2013;Zhao et al., 2011). These complexes are, thereby, becoming a cause for concern due to their environmental persistence and toxicity (Cuprys et al., 2018a;Guerra et al., 2016;Khurana et al., 2021;Pulicharla et al., 2015). ...
... It is evident, that the trivalent cation (Al (III)) showed a higher formation constant with Imipenem than bivalent alkaline earth metals (Mg (II) and Ca (II)) and transition metals (Cu (II) and Fe (II)), which can be attributed to its higher charge density (smaller cationic radius with higher ionic charge). High polarizing metals (or hard Lewis's acids) result in more stable complexes by favouring closer proximity of the metal ion to negatively charged ligands, resulting in a greater force of attraction, owing to its small size and high surface charge (Khurana et al., 2021;Uivarosi, 2013). For bivalent metal ions, alkaline earth metals (Mg (II) and Ca (II)) (K = 3.59 × 10 2 ) were observed to form more stable complexes with Imipenem, compared to transition metals Cu (II) and Fe (II) with stability constants 77.98 and 2.82, respectively. ...
