ORIGINAL RESEARCH Green synthesis, antibacterial activity, and SAR of some novel naphthalimides and allylidenes Garima Kumari • Ramendra K. Singh Received: 4 December 2013 / Accepted: 17 June 2014 / Published online: 5 July 2014 Ó Springer Science+Business Media New York 2014 Abstract Several new cyclic and acyclic naphthalimide and allylidene derivatives have been synthesized following the conventional and microwave synthetic methods and evaluated for their antibacterial activity against a variety of bacterial strains, like B. subtilis (NCIM-2156), S. aureus (NCIM-2079), S. epidermis (NCIM-2493), P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and P. vulgaris (NCIM 2027) following broth dilution method using cip- rofloxacin and vancomycin as reference. All compounds showed MIC values in the range of \0.65–80 lg/mL concentration. Compound 6 showed the maximum anti- bacterial activity (MIC \0.65 lg/mL) almost equivalent to that of standards used, against all bacterial strains under study. Docking results on representative molecules with DNA topoisomerases I and II revealed the possible mode of action of these molecules. Keywords Naphthalimides Á Allylidenes Á MIC Á Zone of inhibition Á Docking Á Topoisomerase Introduction Naphthalimides constitute a versatile class of compounds, which have been used in a wide variety of research implications. Their most recent applications have been oriented in the field of chemistry, biology, and therapeutics. Substituted 1,8-naphthalimides have been shown to dem- onstrate dramatic anticancer activity (Brana et al., 1980, 1981). They exhibit cytostatic activity through DNA intercalation (Waring et al., 1979), which causes enzymatic blockage and reading errors during the replication process (Wakelin et al., 1990; Saenger, 1983). Moreover, these compounds also possess antibacterial (Filho et al., 1994a, b; Correˆa et al., 1996), antispasmodic (Filho et al., 1995), antifungal (Filho et al., 1996a), and analgesic (Filho et al., 1996b, 1998; Correˆa et al., 1997) properties. Although, cinnamaldehyde has well-known antibacterial and anti- cancer properties, very little is known about allylidenes. The antibiotics used generally inhibit steps in cell wall synthesis, b-lactamases, translation process, etc., Cipro- floxacin is a well-known broad-spectrum antibiotic active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting topoisomerase enzymes necessary to separate the strands of bacterial DNA during replication, thereby inhibiting cell division. Topoisomerases are enzymes that regulate the winding of DNA due to the intertwined nature of its double helical structure. These enzymes bind to either single-stranded or double-stranded DNA and cut the phosphate backbone of the DNA, which allows the DNA to be untangled or unwound, and at the end of these processes, the DNA backbone is resealed again. DNA topoisomerases are the enzymes responsible for controlling and maintaining the topological states of DNA. Hence, topoisomerases have become popular targets for antibacterial drugs. In light of these observations, we synthesized a new series of naphthalimide and allylidene derivatives with cyclic and acyclic appendages bearing imide linkages by both microwave (MW), as well as conventional techniques. MW activation, a non-conventional source of energy has become a very popular and useful technique in organic chemistry since the pioneering work of Gedye et al.,(1986) in 1986. The combination of solvent-free reaction condi- tions and MW irradiation leads to large reductions in G. Kumari Á R. K. Singh (&) Nucleic Acids and Antiviral Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad 211002, India e-mail: singhramk@rediffmail.com 123 Med Chem Res (2015) 24:171–181 DOI 10.1007/s00044-014-1118-6 MEDICINAL CHEMISTRY RESEARCH