Synthesis and Biological Evaluation of Fused Pyrans Bearing Coumarin Moiety as Potent Antimicrobial Agents
Nagamallu Renuka and Kariyappa Ajay Kumar
Post Graduate Department of Chemistry, Yuvaraja’s College
University of Mysore, India
corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
A simple approach for the synthesis of fused pyrans to coumarin moiety is presented. The intramolecular cyclisation of 1-aryl-3-(7-hydroxy-4-methyl-2-oxo-2H-chromen-8-yl)-1H-pyrazole-4-carbaldehydes under reflux conditions at 80ºC afforded fused pyrans in a relatively good yield. The synthesized compounds were characterized by spectral studies and elemental analysis. The new compounds were evaluated in vitro for their antifungal and antibacterial activity against different fungi and bacterium species.
INTRODUCTION
The growing population of antibiotic resistance of bacteria strains as a result of enzymatic inactivation of the drug, modification of target sites and extrusion by efflux has become one of the major tasks to be addressed in the area of research in drug design and discovery (Spratt 1994). The construction of complex molecular architectures that exhibit greater biological potency in a facile and efficient manner remains an overarching goal for chemists. In the recent years, coumarins have attracted great attention because of their synthetic utility as building blocks for the construction of biologically potent molecules. Coumarin derivatives are known to have a wide range of activities such as antioxidant, antimicrobial, anti-HIV, antibiotic, anticancer, muscle relaxant, anti-inflammatory and anticoagulant properties (Murakami et al., 2000).
Pyrazoles have attracted particular interest over the last few decades due to use of such a ring system as the core nucleus in various drugs. This class of compounds represent a key motif which occupy a prime place in medicinal chemistry due to their competence to exhibit antimicrobial (Gilbert et al., 2006), anticancer (Igor Magedov et al., 2007), anti-inflammatory (Nora Bennamane et al., 2008), anticonvulsant ( Ozdemir et al., 2007), antipyretic (Sener et al., 2002), peptide deformylase . . . . . [DOWNLOAD FULLTEXT HERE]
REFERENCES
BARTLETT MJ, TURNER CA, HARVEY JE. 2013, Pd-catalyzed allylic alkylation cascade with dihydropyransL regioselective synthesis of furo[3,2-c]pyrans. Org Lett 15(10): 2430-2433.
BENAAMANE N, NEDJAR-KOLLI B, BENTARZI Y, HAMMAL L, GERONIKAKI A, ELEFTHERIOU P, LAGUNIN A. 2008. Synthesis and in silico biological activity evaluation of new N-substituted pyrazolo-oxazine-2-one systems. Bioorg Med Chem 16: 3059-3066.
CALI P, NAERUM L, MUKHIJA S, HJELMENCRANTZ A. 2004.Isoxazole-3-hydroxamic acid derivatives as peptide deformylase inhibitors and potential antibacterial agents. Bioorg Med Chem Lett 14: 5997-6000.
GILBERT AM, FAILLI A, SHUMSKY J, YANG Y, SEVERIN A, SINGH G, HU W, KEENEY D, PETERSEN PJ, KATZ AH. 2006. Pyrazolidine-3,5-diones and 5-hydroxy-1H-pyrazol-3(2H)-ones, inhibitors of UDP-N-acetylenolpyruvyl glucosamine reductase. J Med Chem 49: 6027-6036.
HAMMAM GAEF, EI-SALAM OIABD, ASHRAF MM, NAGLA HA.2005. Novel fluoro substituted benzo(b)pyran with anti-lung cancer activity. Ind J Chem 44B: 1887-1893.
JUNEK H, AIGNER H. 1973, synthesenmitNitrilen, XXXV. Reaktionen von TetracyanathylenmitHeterocyclen. Chem Ber 106: 914-921.
KUMAR K A, RAI KML, VASANTH KUMAR G, MYLARAPPA BN. 2012. A facile route for the synthesis of ethyl N-aryl-2,6-dioxo-piperid-3-ene-4-carboxylates and their biological activity. Int J Pharm Pharm Sci 4(Suppl 4): 564-568.
LEE YR, WANG X, XIA L.2007.An efficient and rapid synthetic route to biologically interesting pyranochalcone natural products. Molecules 12:1420-1429.
MAGEDOV IV, MANPADI M, SLAMBROUCK SV, STEELANT WFA, ROZHKOVA E, PRZHEVAL SKII NM, SNEZNA R, ALEXANDER K. 2007. Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one step multicomponent synthesis. J Med Chem 50: 5183-5192.
MORIGUCHI T, MATSUURA H, ITAKURA Y, KATSUKI H, SAITO H, NISHIYAMA N. 1997. Allixin, a phytoalexin produced by garlic, and its analogues as novel exogenous substances with neurotrophic activity. Life Sci 61: 1413-1420.
MURAKAMI A, GAO G, OMURA M, YANO M, ITO C, FURUKAWA H, TAKAHASHI D, KOSHIMIZU K, OHIGASHI H. 2000. 1,1-Dimethylallylcoumarins potently suppress both lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in mouse macrophage RAW 264.7 cells. Bioorg Med CheM Lett 10: 59-62.
OTTO HH. 1974. Darstellungeiniger 4H-Pyrano[2,3-c]pyrazolderivate. Arch Pharm 307: 444-447.
OZDEMIR Z, KANDILCI HB, GUMUSEL B, CALIS U, BILGIN AA. 2007. Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 42: 373-379.
RENUKA N, KUMAR KA. 2013. Synthesis and biological evaluation of novel Formyl-Pyrazoles bearing Coumarin moiety as potent antimicrobial and antioxidant agents. Bioorg Med Chem Lett. 23: 6406-6409.
SENER A, SENER MK, BILDMCI I, KASIMOGULLARI R,AKCAMUR Y. 2002.Studies on the reactions of cyclic oxalyl compounds with hyrazines or hydrazones: Synthesis and reactions of 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid. J Heterocycl Chem 39: 869-875.
SPRATT BG. 1994. Resistance to antibiotics mediated by target alterations. Science 264: 388-393.
WANG X-S, ZHOU J-X, ZENG Z-S, LI Y-L, SHI D-Q, TU S-J. 2006. One-pot synthesis of pyrano[3,2-c]pyran derivatives catalyzed by KF/Al2O3. Arkivoc (xi): 107-113.
