ORIGINAL RESEARCH Synthesis, X-ray characterization and biological evaluation of some new 2-(4-methy-2-oxo-2H-chromen-7yloxy) acetamide derivatives Bhagavathula S. Diwakar • B. Govindh • Y. Nagendra Sastry • D. S. V. G. K. Kaladhar • Y. L. N. Murthy Received: 20 December 2013 / Accepted: 11 August 2014 Ó Springer Science+Business Media New York 2014 Abstract Newly designed coumarinyloxy acetamide derivatives (7a–7n) were synthesized in good yields and characterised by advanced spectroscopic studies and the XRD studies indicated that no polymorphism is observed in the molecules. Synthesized coumarinyloxy acetamides showed potent antimicrobial activity on human pathogens. Some of the analogues were found to have comparable or even more potency than the standard drugs (Ciprofloxacin for bacteria and Griseofulvin for dermatophytic fungi). Aromatic cou- marinyloxy amides possess good antimicrobial activity fol- lowed by alicyclic compounds but aliphatic straight chain coumarinyloxy amides showed poor antimicrobial activity. In vitro results were correlated with docking studies. Keywords Coumarinyloxy acetamides  Antimicrobial  Docking  Human pathogens Introduction Coumarin is a simple molecule and many of its deriva- tives have been known for more than a century. Coumarin and coumarin-related compounds have proved for many years to have significant therapeutic potential (Lacy and O’Kennedy, 2004). They come from a wide variety of natural sources and new coumarin derivatives are being discovered or synthesised on a regular basis. Their physiological, antimicrobial (Balaji et al., 2013; Smyth et al., 2009), anti-cancer (Kostova, 2005) and anti- inflammatory (Curini et al., 2006; Ghate et al., 2005) antioxidant (Nicolaides et al., 1998; Litinadj et al., 2004) activities make these compounds attractive for further backbone derivatisation and screening as novel thera- peutic agents. In recent years, multiple drug resistance has been developed due to indiscriminate use of existing antimi- crobial drugs in the treatment of infectious diseases and has become a global public health problem (WHO document WHO/CDS/CSR/RMD/, 2003). The antibacterial proper- ties of coumarins were first recognised in 1945 when Goth et al. conducted an investigation with dicoumarol and it was found to inhibit the growth of several strains of bac- teria (Goth, 1945). (Smyth et al., 2009) reported that antimicrobial activity of 43 natural and synthetic couma- rins on clinical isolates of methicillin resistant Staphylo- coccus aureus (MRSA) strains and also demonstrated their resistance modifying activity (RMA). Development of to- poisomerases targeted molecules has great importance to overcome the drug resistance. Drugs that target topoiso- merase I and II have become important for both cancer and bacterial therapy (Teicher, 2008; Pommier and Cushman, 2009; Larsen et al., 2003). A few antibiotics with the coumarin skeleton as part of their structure have been isolated. The most active of them is novobiocin, isolated from Streptomyces niveus, which is mainly active against Gram-positive bacteria (Kawase et al., 2001). These cou- marin antibiotics are potent inhibitors of DNA replication This article is a part of Diwakar’s PhD thesis work. Electronic supplementary material The online version of this article (doi:10.1007/s00044-014-1230-7) contains supplementary material, which is available to authorized users. B. S. Diwakar  B. Govindh  Y. L. N. Murthy (&) Department of Organic Chemistry, Andhra Unversity, Visakhapatnam 530 003, India e-mail: murthyyln@gmail.com Y. Nagendra Sastry  D. S. V. G. K. Kaladhar Department of BioChemistry and Bioinformatics, Gitam University, Visakhapatnam 530 045, India 123 Med Chem Res DOI 10.1007/s00044-014-1230-7 MEDICINAL CHEMISTR Y RESEARCH