ABSTRACT
The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562-3.125 µg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.
Subject(s)
Antitubercular Agents/chemical synthesis , Bacterial Proteins/chemistry , Enzyme Inhibitors/chemical synthesis , Fullerenes/chemistry , Hypoxanthine Phosphoribosyltransferase/chemistry , Mycobacterium tuberculosis/chemistry , Quinazolinones/chemistry , Amino Acid Sequence , Antitubercular Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Catalytic Domain , Cations , Enzyme Inhibitors/pharmacology , Hypoxanthine Phosphoribosyltransferase/antagonists & inhibitors , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Sequence Data , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/enzymology , Protein Binding , Sequence Alignment , Structural Homology, Protein , Structure-Activity Relationship , ThermodynamicsABSTRACT
A series of novel cationic fullerene derivatives bearing a substituted-quinazolin-4(3H)-one moiety as a side arm were synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinones. The synthesized compounds 5a-f were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H37RV) and antimicrobial activity against selected Gram-positive (Staphylococcus aureus and S. pyogenes) and Gram-negative (Pseudomonas aeruginosa, Klebsiella pneumonia and Escherichia coli) bacterial and fungal strains (Candida albicans, Aspergillus clavatus, and A. niger), respectively. All the compounds exhibited significant activity, with the most effective compounds having MIC values and zones of inhibition comparable to those of standard drugs.
Subject(s)
Antifungal Agents/chemical synthesis , Antitubercular Agents/chemical synthesis , Fullerenes/chemistry , Nanoparticles/chemistry , Quinazolines/chemical synthesis , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Aspergillus/drug effects , Candida albicans/drug effects , Cations , Drug Design , Fullerenes/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Microscopy, Electron, Transmission , Mycobacterium tuberculosis/drug effects , Quinazolines/chemistry , Quinazolines/pharmacology , Surface PropertiesABSTRACT
In the present investigation, we describe some novel calixarene based heterocyclic compounds (5a-5i) in which 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives have been coupled with 5,11,17,23-tetra-tert-butyl-25,27-bis(chlorocarbonyl-methoxy)-26,28-dihydroxy calix[4]arene. All the newly synthesized calixarene based heterocyclic compounds have been characterized by elemental analysis and various spectroscopic methods like FTIR, (1)H NMR, (13)C NMR, and FAB-MS. All the final scaffolds have been subjected to antioxidant activity, in vitro antimicrobial screening against two gram (+ve) bacteria (S. aureus, S. pyogenes), two gram (-ve) bacteria (E. coli, P. aeruginosa) and two fungal strains (C. albicans, A. clavatus) and also have been screened for their antitubercular activity against Mycobacterium tuberculosis H(37)Rv.
Subject(s)
Calixarenes/chemistry , Oxadiazoles/chemistry , Thiadiazoles/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Viability/drug effects , Molecular Structure , Oxadiazoles/pharmacology , Structure-Activity Relationship , Thiadiazoles/pharmacologyABSTRACT
A highly selective and sensitive PVC membrane, containing phenylurea substituted calix[4]arene was found to be a suitable ionophore for monohydrogen phosphate (HPO(4)(2-)) ions that exhibited a Nernstian response (with a slope of -29.4 ± 0.3 mV decade(-1)). The working concentration range of the electrode was 6.0 × 10(-8)-1.0 × 10(-1) mol L(-1) with a detection limit of 2.0 × 10(-8) mol L(-1). The response time of the sensor in the whole concentration range is very short (<8s), with a considerable lifetime of at least 15 weeks. The sensor possesses the advantages of short response time, low detection limit and a high selectivity towards a large number of inorganic anions. The developed sensor was used as an indicator electrode in potentiometric titration of monohydrogen phosphate ion with barium chloride. The proposed sensor was successfully applied for the direct determination of monohydrogen phosphate in real life samples.
ABSTRACT
We found that the PVC membrane, containing azo calix[4]arene is a suitable ionophore, exhibited a Nernstian response for neodymium (Nd(3+)) ions (with slope of 19.8±0.2 mV decade(-1) for the triply charged ion) over a wide linear range of 4.0×10(-8) to 1.0×10(-1) mol L(-1) with a detection limit 1.0×10(-8) mol L(-1), a relatively fast response time, in the whole concentration range (<10 s), and a considerable life time at least for four months in the pH range of 4.0-8.0. Furthermore, the electrode revealed high selectivity with respect to all the common alkali, alkaline earth, transition and heavy metal ions, including the members of the lanthanide family other than Nd(3+). Concerning its applications, it was effectively employed for the determination of neodymium ions in industrial waste water as well as in lake water.
