1,8-naphthyridine derivatives: an updated review on recent advancements of their myriad biological activities.

Among all nitrogen-containing heterocycles, the 1,8-naphthyridine scaffold has recently gained an immense amount of curiosity from numerous researchers across fields of medicinal chemistry and drug discovery. This new attention can be ascribed to its versatility of synthesis, its reactiveness and the variety of biological activities it has exhibited. Over the past half-decade, numerous diverse biological evaluations have been conducted on 1,8-naphthyridine and its derivatives in a quest to unravel novel pharmacological facets to this scaffold. Its potency to treat neurodegenerative and immunomodulatory disorders, along with its anti-HIV, antidepressant and antioxidant properties, has enticed researchers to look beyond its broad-spectrum activities, providing further scope for exploration. This review is a consolidated update of previous works on 1,8-naphthyridines and their analogs, focusing on the past 5 years.

Design of nalidixic acid­vanadium complex loaded into chitosan hybrid nanoparticles as smart strategy to inhibit bacterial growth and quorum sensing.

The discovery of new alternatives for the treatment of infectious diseases has become the focus of burgeoning global interest. The complexation of the wide-spectrum antibiotic nalidixic acid (NA) with oxidovanadium(IV) ion and its incorporation into hybrid nanoparticulate systems were explored. The V-NA complex proved to be a stronger antimicrobial agent against E. coli, B. cereus, S. aureus and P. aeruginosa than NA, based on inhibition experiments. Myristyl myristate nanostructured lipid carriers (NLCs) and polymeric nanoparticles of Eudragit NE30D (EuNPs) were hybridized with chitosan (chi) to increase their stability and mucoadhesivity. They showed V-NA encapsulation of 97.8 ± 0.5% and 96.1 ± 0.1% respectively. TEM and DLS characterization ascertained the presence of spherical positive charged NPs ranging from 170 to 330 nm. Controlled release of V-NA from NPs was observed with 30-40% release in 3 days. A considerable potentiation of V-NA antimicrobial activity from 5 to 10 times was elucidated against P. aeruginosa with MIC values of 59.3 and 129.9 µM for NLC/chi and EuNPs/chi respectively, in comparison with 625 µM of the free complex. Hybrid NPs were able to interfere with the quorum sensing of the reporter Chromobacterium violaceum. Cytotoxicity on mouse fibroblast L929 cells was evaluated in the range of 29.7-519 µM by MTT assay showing that, NLC/chi particles supported cell growth in the range of at 29.7-60 µM while Eu/chi do not exert cytotoxicity between 29.7 and 120 µM. These results suggest that nanoparticles are suitable systems for drug delivery applications.

Characterization of a novel polymeric prodrug of an antibacterial agent synthesized by mechanochemical solid-state polymerization.

Polycrystalline methacryloyl monomers of the antibacterial drug nalidixic acid with an anhydride bond to the drug carboxyl group were prepared. The physicochemical properties of the synthesized vinyl monomer were characterized using X-ray powder diffraction, thermal analysis, and polarized light microscopy measurements. Mechanochemical solid-state polymerization of the resulting monomers was carried out to yield a novel polymeric prodrug. The in vitro hydrolysis behavior of the polymeric prodrug indicated that the release rate of drug from the polymeric prodrug was clearly dependent on the pH value of the hydrolysis solution. Moreover, sustained release of the drug at an almost constant rate for more than 10 hr was shown in both neutral and alkaline solutions. The results suggest that anhydride-based polymeric prodrugs could be potentially useful in colon targeted drug delivery systems.

Structure, DNA/proteins binding, docking and cytotoxicity studies of copper(II) complexes with the first quinolone drug nalidixic acid and 2,2'­dipyridylamine.

This work presents the synthesis, structural characterization and biological affinity of the newly synthesized copper(II) complexes with the first antibacterial quinolone drug nalidixic acid (nal) or N-donor ligand 2,2'­dipyridylamine (bipyam). [Cu(II)(nal)(bipyam)Cl], (2) reveals a distorted square pyramidal based geometry in Cu(II) atom confirmed by X-ray crystallography technique. The theoretical stabilities and optimized structures of the complex were obtained from DFT calculations. The ability of the complexes to bind with calf thymus DNA (CT DNA) were investigated by electronic absorption, fluorescence, circular dichroism, and viscosity measurements techniques. The experimental results reveal that the complexes strongly interact with CT DNA via intercalative mode but complex 2 exhibits the highest affinity giving Kb=3.91±0.13×106, M-1. The fluorescence spectroscopy measurements show that both complexes have the superior ability to the replacement of EtBr from DNA-bound EtBr solution and bind to DNA through intercalative mode. Both complex also shows the superior affinity towards proteins with comparatively high binding constant values which have been further revealed by fluorescence spectroscopy measurements. Molecular docking analysis indicates that the interaction of the complexes and proteins are stabilized by hydrogen bonding and hydrophobic interaction. Furthermore, the results of in vitro cytotoxicity reveal that the complex 2 has excellent cytotoxicity than 1 against human breast cancer cell lines (MCF-7).

Poly(methacrylic acid)-modified medical cotton gauzes with antimicrobial and drug delivery properties for their use as wound dressings.

Medical cotton gauzes were modified by grafting poly(methacrylic acid) (PMAA) via free radical polymerization to obtain wound dressings with antimicrobial and drug delivery properties. The effect of several reaction parameters including monomer and initiator concentrations, reaction time, and temperature was studied. The grafting was confirmed by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), swelling studies, and scanning electron microscopy (SEM). The grafted cotton gauzes (gauze-g-PMAA) samples were loaded with ZnO nanoparticles to endow with antibacterial properties. Also, they were tested as drug eluting systems using nalidixic acid as antimicrobial agent. The antibacterial activity of the ZnO-loaded gauze-g-PMAA samples was evaluated against Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis). The PMAA-grafted gauzes showed antibacterial activity and inhibited the growth of both microorganisms. These results suggest that the PMAA-grafted cotton gauzes could be used in the biomedical area particularly as antimicrobial and drug-eluting wound dressings.

Characterisation of OXA-258 enzymes and AxyABM efflux pump in Achromobacter ruhlandii.

OBJECTIVES: The aim of this study was to characterise OXA-258 variants and other features that may contribute to carbapenem resistance in Achromobacter ruhlandii. METHODS: Kinetic parameters for purified OXA-258a and OXA-258b were determined measuring the rate of hydrolysis of a representative group of antimicrobial agents. Whole-genome shotgun sequencing was performed on A. ruhlandii 38 (producing OXA-258a) and A. ruhlandii 319 (producing OXA-258b), and in silico analysis of antimicrobial resistance determinants was conducted. Substrates of the AxyABM efflux pump were investigated by inhibition assays using phenylalanine-arginine ß-naphthylamide (PAßN). Outer membrane protein profiles were resolved by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Kinetic measurements of purified OXA-258 variants displayed an overall weak catalytic efficiency toward ß-lactams. A detectable hydrolysis of imipenem was observed. In silico genomic analysis confirmed the presence of 32 and 35 putative efflux pump-encoding genes in A. ruhlandii strains 38 and 319, respectively. Complete sequences for AxyABM and AxyXY efflux pumps, previously described in Achromobacter xylosoxidans, were detected. Decreases in the MICs for chloramphenicol, nalidixic acid and trimethoprim/sulfamethoxazole were observed in the presence of the inhibitor PAßN, suggesting that these antibiotics are substrates of AxyABM. AxyXY-encoding genes of A. ruhlandii 38 and A. ruhlandii 319 displayed 99% identity. No differences were observed in the outer membrane protein profiles. CONCLUSIONS: The contribution of OXA-258 enzymes to the final ß-lactam resistance profile may be secondary. Further studies on other putative resistance markers identified in the whole-genome analysis should be conducted to understand the carbapenem resistance observed in A. ruhlandii.

A strain of Streptomyces sp. isolated from rhizospheric soil of Crataegus oxycantha producing nalidixic acid, a synthetic antibiotic.

AIM: Exploration of microbes isolated from rhizospheric soil of Crataegus oxycantha for bioactive natural products. METHODS AND RESULTS: A strain of Streptomyces sp. (C-7) was isolated from rhizospheric soil of C. oxycantha. The 16S rRNA gene sequence of strain C-7 displayed 99% sequence similarity with different Streptomyces species. The highest score was displayed for Streptomyces sp. strain Chy2-8 followed by Streptomyces violarus strain NBRC13104 and Streptomyces arenae strain ISP5293. The position of C-7 in the phylogenetic tree suggested uniqueness of the strain. Nalidixic acid (1), a quinolone antibiotic, was isolated from Streptomyces sp. strain (C-7) for the first time and characterized by NMR and chemically analysed. Compound 1 exhibited antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. The production of compound 1 was also validated by repeating fermentation of strain C-7 and compound isolation in a separate natural product laboratory with no prior information. Furthermore, Compound 1 showed a cytotoxic effect against human prostate cancer cell line PC3 with an IC50 11 µg ml-1 . CONCLUSION: To the best of our knowledge, this is the first report showing production of nalidixic acid naturally by a strain of Streptomyces sp. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we isolated a strain of Streptomyces sp. producing nalidixic acid, which was otherwise only obtained through chemical synthesis.

A bionanohybrid ZnAl-NADS ecological pesticide as a treatment for soft rot disease in potato (Solanum tuberosum L.).

Pectobacterium carotovorum (Pc) is a phytopathogenic strain that causes soft rot disease in potato (Solanum tuberosum L.), resulting in postharvest losses. Chemical control is effective for managing this disease, but overdoses cause adverse effects. Because farmers insist on using chemical agents for crop protection, it is necessary to develop more effective pesticides in which the active compound released can be regulated. In this context, we proposed the synthesis of ZnAl-NADS, in which nalidixic acid sodium salt (NADS) is linked to a ZnAl-NO3 layered double hydroxide (LDH) host as a nanocarrier. XRD, FT-IR, and SEM analyses confirmed the successful intercalation of NADS into the interplanar LDH space. The drug release profile indicated that the maximum release was completed in 70 or 170 min for free NADS (alone) or for NADS released from ZnAl-NADS, respectively. This slow release was attributed to strong electrostatic interactions between the drug and the anion exchanger. A modulated release is preferable to the action of the bulk NADS, showing increased effectiveness and minimizing the amount of the chemical available to pollute the soil and the water. The fitting data from modified Freundlich and parabolic diffusion models explain the release behavior of the NADS, suggesting that the drug released from ZnAl-NADS bionanohybrid was carried out from the interlamellar sites, according to the ion exchange diffusion process also involving intraparticle diffusion (coeffect). ZnAl-NADS was tested in vitro against Escherichia coli (Ec) and Pc and exhibited bacteriostatic and biocidal effects at 0.025 and 0.075 mg mL-1, respectively. ZnAl-NADS was also tested in vivo as an ecological pesticide for combating potato soft rot and was found to delay typical disease symptoms. In conclusion, ZnAl-NADS can potentially be used to control pests, infestation, and plant disease.

Drug repurposing: An approach to tackle drug resistance in S. typhimurium.

Drug resistant S. typhimurium pose important public health problem. The development of effective drugs with novel mechanism(s) of action is needed to overcome issues pertaining to drug resistance. Drug repurposing based on computational analyses is considered a viable alternative strategy to circumvent this issue. In this context, 1309 FDA-approved drugs molecules from Mantra 2.0 database were analyzed for this study, against S. typhimurium. Sixteen compounds having similar profiles of gene expression as quinolones were identified from the database, Mantra 2.0. Further, the pharmacophore characteristics of each resultant molecule were identified and compared with the features of nalidixic acid, using the PharamGist program. Subsequently, the activities of these compounds against S. typhimurium DNA gyrase were identified, using molecular docking study. Side effects analysis was also performed for the identified compounds. Molecular dynamics simulation was carried out for the compound to validate its binding efficiency. Further, characterization of screened compound revealed IC50 values in micromolar concentration range, of which flufenamic acid showed comparable in vitro activity alongside ciprofloxacin and nalidixic acid. Thus represent interesting starting points for further optimization against S. typhimurium infections. It may be noted that the results we have obtained are the first experimental evidence of flufenamic acid activity against S. typhimurium.

Factors affecting the roles of reactive species in the degradation of micropollutants by the UV/chlorine process.

The UV/chlorine process is an emerging advanced oxidation process (AOP) that produces various reactive species, such as hydroxyl radicals (HO) and reactive chlorine species (RCS). The effects of the treatment conditions, such as chlorine dosage and pH, and the water matrix components of natural organic matter (NOM), alkalinity, ammonia and halides, on the kinetics and reactive species in the degradation of four micropollutants, metronidazole (MDZ), nalidixic acid (NDA), diethyltoluamide (DEET) and caffeine (CAF), by the UV/chlorine process were investigated. The degradation of MDZ and CAF was primarily attributable to HO and ClO, respectively, while that of NDA was primarily attributable to both ClO and CO3-. HO, Cl and CO3- are important for the degradation of DEET. The second-order rate constants for ClO with CAF and CO3- with NDA were determined to be 5.1 (±0.2) × 107 M-1s-1 and 1.4 (±0.1) × 107 M-1s-1, respectively. Increasing chlorine dosage slightly changed the contribution of HO but linearly increased that of ClO to micropollutant degradation. Increasing pH decreased the contribution of either HO or Cl but not that of ClO. Both NOM and bicarbonate decreased the contributions of HO and Cl, whereas NOM but not bicarbonate significantly decreased that of ClO. The contribution of either HO or Cl first rose and then fell as the molar ratio of ammonia to chlorine increased from 0 to 1:1, while that of ClO decreased. The co-presence of high concentrations of Cl- and Br- enhanced the contribution of ClBr- and BrCl.

Enhancing the Potency of Nalidixic Acid toward a Bacterial DNA Gyrase with Conjugated Peptides.

Quinolones and fluoroquinolones are widely used antibacterial agents. Nalidixic acid (NA) is a first-generation quinolone-based antibiotic that has a narrow spectrum and poor pharmacokinetics. Here, we describe a family of peptide-nalidixic acid conjugates featuring different levels of hydrophobicity and molecular charge prepared by solid-phase peptide synthesis that exhibit intriguing improvements in potency. In comparison to NA, which has a low level of potency in S. aureus, the NA peptide conjugates with optimized hydrophobicities and molecular charges exhibited significantly improved antibacterial activity. The most potent NA conjugate-featuring a peptide containing cyclohexylalanine and arginine-exhibited efficient bacterial uptake and, notably, specific inhibition of S. aureus DNA gyrase. A systematic study of peptide-NA conjugates revealed that a fine balance of cationic charge and hydrophobicity in an appendage anchored to the core of the drug is required to overcome the intrinsic resistance of S. aureus DNA gyrase toward this quinolone-based drug.

An Infection-Responsive Approach To Reduce Bacterial Adhesion in Urinary Biomaterials.

Infection is an inevitable consequence of chronic urinary catheterization with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterized patients. In this work, we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for "intelligent" antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalized nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7 and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development toward the prevention of catheter-associated urinary tract infections in vivo.

New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges.

A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a-c. The chemical structures of the new Schiff bases (5b and 5d-h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%-42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition) at the same concentration (10 µM). The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a-c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

Integrated In Silico-In Vitro Discovery of Lung Cancer-related Tumor Pyruvate Kinase M2 (PKM2) Inhibitors.

BACKGROUND: The tumor pyruvate kinase M2 (PKM2) is involved in the glycolytic pathway of lung cancer and targeting this kinase has been observed to radiosensitize non-small cell lung cancer (NSCLC). OBJECTIVE: An integration of in silico virtual screening and in vitro kinase assay was described to discover novel PKM2 inhibitors from a candidate library containing >400,000 commercially available compounds. METHOD: The method is a stepwise screening scheme that first used empirical strategies to fast exclude those undruggable compounds in the library and then employed molecular docking and molecular dynamics (MD)-based rescoring to identify few potential hits. Subsequently, the computational findings were substantiated using a standard kinase assay protocol. RESULTS: Four compounds, i.e. nalidixic acid, indoprofen, hematoxylin and polydatin, were identified to inhibit PKM2 kinase at micromolar level, with IC50 values of 53, 21, 340 and 128 .M, respectively. CONCLUSION: Structural analysis revealed that hydrogen bonds, salt bridges, π-π stacking and hydrophobic forces co-confer high stability and strong specificity to PKM2-inhibitor binding.

Effect of poly ethylene glycol on the mechanical and thermal properties of bioactive poly(ε-caprolactone) melt extrudates for pharmaceutical applications.

This paper investigates the effects of polyethylene glycol (PEG), on the mechanical and thermal properties of nalidixic acid/poly ε-caprolactone (NA)/PCL blends prepared by hot melt extrusion. The blends were characterized by tensile and flexural analysis, dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis and X-ray diffraction. Results show that loading PEG in the PCL had a detrimental effect on the tensile strength and toughness of the blends, reducing them by 20-40%. The partial miscibility of the PCL-PEG system, causes an increase in Tg. While increases in the crystallinity is attributed to the plasticisation effect of PEG and the nucleation effect of NA. The average crystal size increased by 8% upon PEG addition. Experimental data indicated that the addition of NA caused loss of the tensile strength and toughness of PCL. Thermal analysis of the PCL showed that on addition of the thermally unstable NA, thermal degradation occurred early and was autocatalytic. However, the NA did benefit from the heat shielding provided by the PCL matrix resulting in more thermally stable NA particles.

Re-engineering nalidixic acid's chemical scaffold: A step towards the development of novel anti-tubercular and anti-bacterial leads for resistant pathogens.

Occurrence of antibacterial and antimycobacterial resistance stimulated a thrust to discover new drugs for infectious diseases. Herein we report the work on re-engineering nalidixic acid's chemical scaffold for newer leads. Stepwise clubbing of quinoxaline, 1,2,4-triazole/1,3,4-oxadiazole with nalidixic acid yielded better compounds. Compounds were screened against ciprofloxacin resistant bacteria and Mycobacterium tuberculosis H37Rv species. Results were obtained as minimum inhibitory concentration, it was evident that molecule with quinoxaline linked azide as side chain served as antitubercular lead (<6.25 µg/ml) whilst molecule with oxadiazole or triazole linked quinoxaline side chain served as anti-bacterial lead. Few compounds were significantly active against Escherichia coli and Proteus vulgaris with MIC less than 0.06 µg/ml and relatively potent than ciprofloxacin. No true compound was potentially active against Salmonella species as compared to amoxicillin.

Oxidative degradation of nalidixic acid by nano-magnetite via Fe2+/O2-mediated reactions.

Organic pollution has become a critical issue worldwide due to the increasing input and persistence of organic compounds in the environment. Iron minerals are potentially able to degrade efficiently organic pollutants sorbed to their surfaces via oxidative or reductive transformation processes. Here, we explored the oxidative capacity of nano-magnetite (Fe3O4) having ∼ 12 nm particle size, to promote heterogeneous Fenton-like reactions for the removal of nalidixic acid (NAL), a recalcitrant quinolone antibacterial agent. Results show that NAL was adsorbed at the surface of magnetite and was efficiently degraded under oxic conditions. Nearly 60% of this organic contaminant was eliminated after 30 min exposure to air bubbling in solution in the presence of an excess of nano-magnetite. X-ray diffraction (XRD) and Fe K-edge X-ray absorption spectroscopy (XANES and EXAFS) showed a partial oxidation of magnetite to maghemite during the reaction, and four byproducts of NAL were identified by liquid chromatography-mass spectroscopy (UHPLC-MS/MS). We also provide evidence that hydroxyl radicals (HO(•)) were involved in the oxidative degradation of NAL, as indicated by the quenching of the degradation reaction in the presence of ethanol. This study points out the promising potentialities of mixed valence iron oxides for the treatment of soils and wastewater contaminated by organic pollutants.

Thermo-mechanical properties of poly ε-caprolactone/poly L-lactic acid blends: addition of nalidixic acid and polyethylene glycol additives.

The search for ideal biomaterials is still on-going for tissue regeneration. In this study, blends of poly ε-caprolactone (PCL) with poly l-lactic acid (PLLA), nalidixic acid (NA) and polyethylene glycol (PEG) were prepared. Mechanical and thermal properties of the blends were investigated by tensile and flexural analysis, DSC, TGA, WXRD, MFI, BET, SEM and hot stage optical microscopy. Results showed that the loading of PLLA caused a significant decrease in tensile strength and almost total eradication of the elongation at break of PCL matrix, especially after PEG and NA addition. Increased stiffness was also noted with additional NA, PEG and PLLA, resulting in an increase in the flexural modulus of the blends. Isothermal degradation indicated that bulk PCL, PLLA and the blends were thermally stable at 200°C for the duration of 2h making extrusion of the blends at this temperature viable. Morphological study showed that increasing the PLLA content and addition of the very low viscosity PEG and powder NA decreased the Melt Flow Indexer and increased the viscosity. At the higher temperature, the PLLA begins to soften and eventually melts allowing for increased flow and, coupling this with, the natural increase in MFI caused by temperature is enhanced further. The PEG and NA addition increased dramatically the pore volume which is important for cell growth and flow transport of nutrients and metabolic waste.

Origins of the Quinolone Class of Antibacterials: An Expanded "Discovery Story".

Published descriptions of the specific lines of research leading to the discovery of therapeutically important medicines, especially major new class medicines, have long provided value to the biopharmaceutical community as models of success, often influencing the strategies and methods of subsequent drug research. Quinolone antibacterials represent one of medicine's most important classes of anti-infective agents; yet in contrast to many other classes of anti-infectives, astonishingly few details concerning the origin of the class or the rationale leading to the selection of the first clinical agent, nalidixic acid, were ever published by the discoverers. Moreover, earlier disclosures of an independent discovery of the quinolone class of antibacterials have been almost entirely overlooked by the scientific literature. This review brings together all the available information from primary literature sources relating to both discoveries and provides for the first time a much fuller, if still partially speculative, story of the earliest years of this important class of drugs.

Molecular organization of nalidixate conjugated calixarenes in bacterial model membranes probed by molecular dynamics simulation and Langmuir monolayer studies.

Two p-tert-butylcalix[4]arene derivatives bearing one or two nalidixic acid groups connected to the lower rim of p-tert-butylcalix[4]arene through the propylenic spacer were studied upon interaction with model bacterial membranes. Indeed, these derivatives were developed recently as new macrocyclic antibiotic carriers for antibacterial therapy. To obtain molecular level information about the interaction between the calixarene conjugates and a membrane lipid, atomistic molecular dynamics simulation, as well as surface pressure, surface potential, polarization modulation infrared reflection-absorption spectroscopy, and Brewster angle microscopy studies of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE)-calixarene derivative films were performed. The results obtained indicate that the interaction between the calixarene derivatives and DMPE occurs via the phosphate and carbonyl groups present in the lipid. Although both calixarene derivatives increase the chain tilt and conformational disordering of the DMPE molecules, these effects are more important in the case of the monosubstituted derivative. Importantly, the two derivatives have an opposite impact on hydration of the phosphoglyceride polar head.