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      Synthesis and Antibacterial Activity of Some Heterocyclic Chalcone Analogues Alone and in Combination with Antibiotics

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          Abstract

          A series of simple heterocyclic chalcone analogues have been synthesized by Claisen Schmidt condensation reactions between substituted benzaldehydes and heteroaryl methyl ketones and evaluated for their antibacterial activity. The structures of the synthesized chalcones were established by IR and 1H-NMR analysis. The biological data shows that compounds p 5 , f 6 and t 5 had strong activities against both susceptible and resistant Staphylococcus aureus strains, but not activity against a vancomycin and methicillin resistant Staphylococcus aureus isolated from a human sample. The structure and activity relationships confirmed that compounds f 5 , f 6 and t 5 are potential candidates for future drug discovery and development.

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          Most cited references30

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          The crisis in antibiotic resistance.

          H Neu (1992)
          The synthesis of large numbers of antibiotics over the past three decades has caused complacency about the threat of bacterial resistance. Bacteria have become resistant to antimicrobial agents as a result of chromosomal changes or the exchange of the exchange of genetic material via plasmids and transposons. Streptococcus pneumoniae, Streptococcus pyogenes, and staphylococci, organisms that cause respiratory and cutaneous infections, and members of the Enterobacteriaceae and Pseudomonas families, organisms that cause diarrhea, urinary infection, and sepsis, are now resistant to virtually all of the older antibiotics. The extensive use of antibiotics in the community and hospitals has fueled this crisis. Mechanisms such as antibiotic control programs, better hygiene, and synthesis of agents with improved antimicrobial activity need to be adopted in order to limit bacterial resistance.
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            Evolution and spread of antibiotic resistance.

            Antibiotic resistance is a clinical and socioeconomical problem that is here to stay. Resistance can be natural or acquired. Some bacterial species, such as Pseudomonas aeruginosa, show a high intrinsic resistance to a number of antibiotics whereas others are normally highly antibiotic susceptible such as group A streptococci. Acquired resistance evolve via genetic alterations in the microbes own genome or by horizontal transfer of resistance genes located on various types of mobile DNA elements. Mutation frequencies to resistance can vary dramatically depending on the mechanism of resistance and whether or not the organism exhibits a mutator phenotype. Resistance usually has a biological cost for the microorganism, but compensatory mutations accumulate rapidly that abolish this fitness cost, explaining why many types of resistances may never disappear in a bacterial population. Resistance frequently occurs stepwise making it important to identify organisms with low level resistance that otherwise may constitute the genetic platform for development of higher resistance levels. Self-replicating plasmids, prophages, transposons, integrons and resistance islands all represent DNA elements that frequently carry resistance genes into sensitive organisms. These elements add DNA to the microbe and utilize site-specific recombinases/integrases for their integration into the genome. However, resistance may also be created by homologous recombination events creating mosaic genes where each piece of the gene may come from a different microbe. The selection with antibiotics have informed us much about the various genetic mechanisms that are responsible for microbial evolution.
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              Synthesis and Applications of Small Molecule Libraries.

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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                01 June 2012
                June 2012
                : 17
                : 6
                : 6684-6696
                Affiliations
                [1 ]Department of Medicinal Chemistry, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Dist. 1, Ho Chi Minh City 70000, Vietnam; Email: thaonhu1986@ 123456yahoo.com (T.-T.-N.N.); ngocphuonght@ 123456yahoo.com (T.-N.-P.H.)
                [2 ]Department of Synthetic/Organic Chemistry, Ton Duc Thang University, Nguyen Huu Tho St., Tan Phong Ward, Dist. 7, Ho Chi Minh City 70000, Vietnam; Email: dtuongha@ 123456yahoo.com
                [3 ]Department of Microbiology, School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, 41 Dinh Tien Hoang, Dist. 1, Ho Chi Minh City 70000, Vietnam; Email: trancdong@ 123456gmail.com
                Author notes
                [* ] Authors to whom correspondence should be addressed; Email: thanhdaot@ 123456yahoo.com or tranthanhdao@ 123456uphcm.edu.vn (T.-D.T.); thaikhacminh@ 123456gmail.com or thaikhacminh@ 123456uphcm.edu.vn (K.-M.T.); Tel.: +84-903-716-482 (T.-D.T.); +84-909-680-385 (K.-M.T.); Fax: +84-8-3822-5435.
                Article
                molecules-17-06684
                10.3390/molecules17066684
                6268422
                22728362
                4babe742-57ea-4424-9af1-35991ee8951e
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 07 May 2012
                : 25 May 2012
                : 30 May 2012
                Categories
                Article

                chalcone,heterocyclic chalcone analogues,synthesis,antibacterial,synergitic activity,antibiotics combination,mrsa

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