Novel antibacterial active quinolone-fluoroquinolone conjugates and 2D-QSAR studies.

Novel, quinolone-fluoroquinolone conjugates 10a-f, 11a-f, 13a-f and 14a-f with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antibacterial bioassay showed the synthesized bis-conjugates exhibit anti-bacterial properties comparable with the parent drugs.

[1]  Aladdin M. Srour,et al.  Rational design, synthesis and molecular modeling studies of novel anti-oncological alkaloids against melanoma. , 2015, Organic & biomolecular chemistry.

[2]  T. Baasov,et al.  Dual-acting hybrid antibiotics: a promising strategy to combat bacterial resistance , 2010, Expert opinion on drug discovery.

[3]  Peter C. Jurs,et al.  Descriptions of molecular shape applied in studies of structure/activity and structure/property relationships , 1987 .

[4]  A. S. Girgis,et al.  Synthesis and QSAR study of novel cytotoxic spiro[3H-indole-3,2'(1'H)-pyrrolo[3,4-c]pyrrole]-2,3',5'(1H,2'aH,4'H)-triones. , 2012, European journal of medicinal chemistry.

[5]  Corwin Hansch,et al.  Role of hydrophobic effects in mechanistic QSAR , 1999 .

[6]  Riham F. George,et al.  Synthesis, hypnotic properties and molecular modeling studies of 1,2,7,9-tetraaza-spiro[4.5]dec-2-ene-6,8,10-triones. , 2011, European journal of medicinal chemistry.

[7]  R Gomeni,et al.  Computer-assisted drug development (CADD): an emerging technology for designing first-time-in-man and proof-of-concept studies from preclinical experiments. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[8]  K. Poole Efflux-Mediated Resistance to Fluoroquinolones in Gram-Negative Bacteria , 2000, Antimicrobial Agents and Chemotherapy.

[9]  A S Ivanov,et al.  Strategy of computer-aided drug design. , 2003, Current drug targets. Infectious disorders.

[10]  Alan R. Katritzky,et al.  Rational design, synthesis, and 2D-QSAR study of anti-oncological alkaloids against hepatoma and cervical carcinoma , 2015 .

[11]  D. Pompliano,et al.  Drugs for bad bugs: confronting the challenges of antibacterial discovery , 2007, Nature Reviews Drug Discovery.

[12]  ElSayed M Shalaby,et al.  Regioselective synthesis, stereochemical structure, spectroscopic characterization and geometry optimization of dispiro[3H-indole-3,2′-pyrrolidine-3′,3″-piperidines] , 2014 .

[13]  Riham F. George,et al.  Stereoselective Synthesis, Structural and Spectroscopic Study of 4,5,11‐Triazatricyclo[6.2.1.0*2,6*]Undec‐5‐ene , 2016 .

[14]  C. Hansch,et al.  Searching for allosteric effects via QSAR. Part II. , 2003, Bioorganic & medicinal chemistry.

[15]  R. Duval,et al.  In vitro activity of para-guanidinoethylcalix[4]arene against susceptible and antibiotic-resistant Gram-negative and Gram-positive bacteria. , 2007, The Journal of antimicrobial chemotherapy.

[16]  I. Khanna,et al.  Structure-activity relationships among DNA gyrase inhibitors. Synthesis and biological evaluation of 1,2-dihydro-4, 4-dimethyl-1-oxo-2-naphthalenecarboxylic acids as 1-carba bioisosteres of oxolinic acid. , 1984, Journal of medicinal chemistry.

[17]  Mary Jane Ferraro,et al.  Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard , 2000 .

[18]  J. Bartlett,et al.  Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  T. Suzuki,et al.  Quinolone antimicrobial agents. 1. Versatile new synthesis of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids. , 1978, Journal of medicinal chemistry.

[20]  Aladdin M. Srour,et al.  Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkers. , 2014, Organic & biomolecular chemistry.

[21]  Christopher T. Walsh,et al.  Antibiotics for Emerging Pathogens , 2009, Science.

[22]  A. Katritzky,et al.  Microwave-Assisted Synthesis of Biotin Conjugates with Quinolone Antibiotics via Amino Acids , 2014, Synthesis.

[23]  S. Arabia,et al.  Aminoacyl Benzotriazolides: Versatile Reagents for the Preparation of Peptides and Their Mimetics and Conjugates. , 2014 .

[24]  L. McDonald,et al.  Emergence of Reduced Susceptibility and Resistance to Fluoroquinolones in Escherichia coliin Taiwan and Contributions of Distinct Selective Pressures , 2001, Antimicrobial Agents and Chemotherapy.

[25]  T. Long,et al.  Trihydroxamate siderophore-fluoroquinolone conjugates are selective sideromycin antibiotics that target Staphylococcus aureus. , 2013, Bioconjugate chemistry.

[26]  Girinath G. Pillai,et al.  Synthesis, and QSAR analysis of anti-oncological active spiro-alkaloids. , 2015, Organic & biomolecular chemistry.

[27]  B. Meunier,et al.  Hybrid molecules with a dual mode of action: dream or reality? , 2008, Accounts of chemical research.

[28]  A. Katritzky,et al.  Quinine bis-conjugates with quinolone antibiotics and peptides: synthesis and antimalarial bioassay. , 2012, Organic & biomolecular chemistry.

[29]  A. Katritzky,et al.  Regioselective synthesis and theoretical studies of an anti-neoplastic fluoro-substituted dispiro-oxindole , 2015 .

[30]  Changqin Hu,et al.  Characterization of clinical Escherichia coli isolates from China containing transferable quinolone resistance determinants. , 2010, The Journal of antimicrobial chemotherapy.

[31]  A. S. Girgis,et al.  Regioselective synthetic approaches towards 1,2,8,9-tetraazadispiro[4.1.4.2]trideca-2,9-dien-6-ones of potential antimicrobial properties. , 2009, European journal of medicinal chemistry.

[32]  Federico Corelli,et al.  The 4-quinolone-3-carboxylic acid motif as a multivalent scaffold in medicinal chemistry. , 2009, Current medicinal chemistry.

[33]  A. Katritzky,et al.  Synthesis and antibacterial evaluation of amino acid-antibiotic conjugates. , 2014, Bioorganic & medicinal chemistry letters.

[34]  G. Superti-Furga,et al.  Rediscovering the sweet spot in drug discovery. , 2003, Drug discovery today.

[35]  Riham F. George,et al.  Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates. , 2015, Bioorganic & medicinal chemistry letters.

[36]  A. Katritzky,et al.  Syntheses of Chiral N‐(Protected) Tri‐ and Tetrapeptide Conjugates , 2012, Chemical biology & drug design.