ORIGINAL RESEARCH Synthesis and evaluation of a series of aminocyanopyridines as antimicrobial agents Aliye Altundas • Selcuk Ayvaz • Elif Logoglu Received: 31 July 2009 / Accepted: 17 September 2009 / Published online: 29 October 2009 Ó Birkha ¨user Boston 2010 Abstract With the aim of developing potential antimi- crobials, a series of 2-amino-3-cyanopyridines incorporat- ing both sulfur and oxygen as part of the heteroaromatic ring (methyl thiophene, methyl furan) and fused cycloalkane groups were synthesized and characterized by FTIR, 1 H-NMR, 13 C-NMR, and bases of elemental analysis. All synthesized compounds were evaluated for their in vitro antibacterial and antifungal activity. Antibacterial and antifungal activities of aminocyanopyridines against Pseu- domonas aeruginosa ATCC 29212, Bacillus subtilis RSKK 244, Bacillus megaterium (clinical isolate), the gram-posi- tive bacterium Micrococcus luteus NRRLB 4375, and the fungus Candida albicans ATCC 90028 were studied. The relationship between the functional-group variation and the biological activity of the evaluated compounds is discussed. Keywords 2-Amino-3-cyanopyridines Á Thiophene Á Furan Á Antimicrobial agents Introduction The use of most antimicrobial agents is limited, not only by rapidly developing drug resistance, but also by the unsat- isfactory results of present treatments of bacterial and fungal infections and side effects (Fidler, 1998). Therefore, the synthesis and investigation of new compounds which possess antimicrobial activity are very important. N NH 2 CN N NH 2 CN R 3 R 2 R 1 2 3 N 1 Many naturally occurring and synthetic compounds containing the pyridine (1) scaffold exhibit interesting pharmacological properties (Chang et al., 2005). Pyridine is one of the most popular N-heteroaromatics incorporated into the structure of many pharmaceuticals. Among these, cya- nopryridines and aminocycanopyridines (2) with different alkyl and aryl groups (3) were found to show antimicrobial (Moussa et al., 1983), antihypertensive (Baldwin et al., 1980), cardiovascular (Krauze et al., 1985), anti-inflam- matory, analgesic, and antipyretic (Manna et al., 1999) properties as well as 1KK-b inhibitor properties (Murata et al., 2004). They are also important as useful intermediates in preparing a variety of biologically active heterocyclic compounds (Deo et al., 1991). The synthesis of 2-amino-3- cycanopyridines (2) has been extensively studied (Taylor and Crovetti, 1954). In the last few decades, a considerable amount of attention has been devoted to the synthesis of 2-amino-3-cycanopyridine derivatives (3) and the study of their biological activities such as antibacterial, antifungal, and inhibitor. 1,4-Dihydropyridines are calcium channel antagonists that produce vascular smooth muscle relaxation (Mayler, 1989). The nature and position of the C4-aryl ring sub- stituent are responsible for the voltage-dependent calcium- channel antagonist activity. In general, the presence of an aryl group at C4, and of esters, acyl, sulfonyl, or nitrile groups at C3 and C5, of 1,4-dihydropyridine has proved to A. Altundas (&) Á S. Ayvaz Á E. Logoglu Department of Chemistry, Faculty of Arts and Sciences, Gazi University, 06500 Ankara, Teknikokullar, Turkey e-mail: aaltundas@gazi.edu.tr 123 Med Chem Res (2011) 20:1–8 DOI 10.1007/s00044-009-9273-x MEDICINAL CHEMISTR Y RESEARCH