Indian Journal of Chemistry Vol. 52B, December 2013, pp 1493-1499 Synthesis and antimicrobial activity of pyrazolinone and pyrazole analogues containing quinoline moiety Mohd Amir*, Sadique A Javed & Mohd Zaheen Hassan Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi 110 062, India E-mail: mamir_s2003@yahoo.co.in Received 11 February 2013; accepted (revised) 19 July 2013 A new class of quinoline derivatives containing pyrazoline-5-one and pyrazole moiety (3a-j and 4a-j) have been synthesized by condensation of various oxobutyrates/pentane-2,4-dione derivatives with 8-quinolinoxyacetic acid hydrazide. Elemental analysis, IR, 1 H NMR and mass spectral data support the structures of the newly synthesized compounds. The synthesized compounds have been evaluated for their antimicrobial activity against S. aureus, E. coli, A. niger and C. albicans using serial plate dilution method. Compound 4-(2-(4-fluorophenyl)hydrazono)-3-methyl-1-(2-(quinolin-8-yloxy) acetyl)-1H-pyrazol-5(4H)-one 3f having log P 1.52 has emerged as the most potent antimicrobial agent of the series. Keywords: Quinoline, pyrazolinone, pyrazole, antimicrobial activity Over the years, a wide range of antimicrobial agents have been discovered which prolonged the lifespan and eased the affliction of million peoples but unfortunately microbial resistance resulted in a dwindling pool of effective antibiotics 1 . Emergence of bacterial resistance toward a number of antimicrobial agents such as -lactam antibiotics, macrolides, quinolones, and vancomycin is becoming a major worldwide health problem. The most significant problem in clinical practice is increased isolation of methicillin-resistant Staphylococcus aureus (MRSA) strains 2 . Similarly, in the past few years, gram negative E. coli have become increasingly resistant to most frontline antibiotics, including third generation cephalosporins, aminoglycosides, and even quino- lones 3-5 . Resistance to existing antifungal agents is also a major threat in patients with compromised host defenses, such as cancer patients and those receiving haematopoietic stem cell transplants 6,7 . Therefore, there is a pressing need for development of new antimicrobial agents which may be effective against the resistant microbes. Quinolines play a unique role in drug discovery programs. Quinolines for instance, ciprofloxacin (Figure 1), norfloxacin, levofloxacin and moxi- floxacin are being marketed as imperative broad spectrum antibiotics for the treatment of microbial infections 8 . Various quinoline derivatives are also reported to exhibit a wide spectrum of biological properties such as antimicrobial 9,10 , antimalarial 11 , and antitubercular activities 12-14 . Pyrazoles and pyrazoline- 5-ones are also an important class of heterocyclic compounds showing wide range of biological activities such as antimicrobial 15,16 (Figure 1), anti- tubercular 17,18 and anti-inflammatory activities 19,20 . On the basis of these observations herein is reported the synthesis of 3-methyl-4-(2-arylhydrazono)-1-(2- (quinolin-8-yloxy)acetyl)-1H-pyrazol-5(4H)-ones 3a-j and 1-(3,5-dimethyl-4-(aryldiazenyl)-1H-pyrazol-1- yl)-2-(quinolin-8-yloxy)ethanones 4a-j in which it is explored if the hybrid pyrazolone/pyrozolyl-quinoline scaffold could have a synergistic feature useful to improve the antimicrobial efficacy. Results and Discussion Twenty new compounds 3a-j and 4a-j were prepared as depicted in Scheme I. The reactions of aryldiazonium chlorides with ethyl acetoacetate and acetylacetone in presence of sodium acetate yielded the corresponding ethyl-2-(aryl hydrazono)-3-oxo- butyrates 1a-j and 3-aryl diazenyl pentane-2,4-dione 2a-j. 8-Quinolinoxyacetic acid hydrazide (QAAH) was prepared by the reaction of 8-hydroxyquinoline with ethyl chloroacetate followed by treatment with hydrazine hydrate. Reactions of compounds 1a-j with QAAH in presence of glacial acetic acid resulted in the formation of 3-methyl-4-(2-arylhydrazono)-1-(2- (quinolin-8-yloxy)acetyl)-1H-pyrazol-5(4H)-one, 3a-j.