Membrane fusion, an integral event in several biological processes, is characterized by several intermediate steps guided by specific energy barriers. Hence, it requires the aid of fusogens to complete the process. Common fusogens, such as proteins/peptides, have the ability to overcome theses barriers by their conformational reorganization, an advantage not shared by small drug molecules. Hence, drug induced fusion at physiologically relevant drug concentrations is rare and occurs only in the case of the oxicam group of non steroidal anti-inflammatory drugs (NSAIDs). To use drugs to induce and control membrane fusion in various biochemical processes requires the understanding of how different parameters modulate fusion. Also, fusion efficacy needs to be enhanced. Here we have synthesized and used Cu(II) complexes of fusogenic oxicam NSAIDs, Meloxicam and Piroxicam, to induce fusion in model membranes monitored by using DSC, TEM, steady-state, and time-resolved spectroscopy. The ability of the complexes to anchor apposing model membranes to initiate/facilitate fusion has been demonstrated. This results in better fusion efficacy compared to the bare drugs. These complexes can take the fusion to its final step. Unlike other designed membrane anchors, the role of molecular recognition and strength of interaction between molecular partners is obliterated for these preformed Cu(II)-NSAIDs.

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Besides their principal functions as painkillers and anti-inflammatory agents, drugs belonging to the nonsteroidal anti-inflammatory drug (NSAID) group also have anticancer properties. Cu(II) complexes of these drugs enhance the anticancer effect. How they exert this effect is not clear. As a possible molecular mechanism, our group has already shown that the Cu(II) complexes of two oxicam NSAIDs with anticancer properties, viz. piroxicam and meloxicam, can directly bind to the DNA backbone. AT stretches are abundant in the eukaryotic genome. These stretches are more accessible to binding of different ligands, resulting in expression of different functions. AT stretches containing both alternating base pairs and homopolymeric bases in individual strands show subtle differences in backbone structures. It is therefore of interest to see how the Cu(II)-NSAID complexes respond to such differences in backbone structure. Binding studies of these complexes with alternating polydA-dT and homopolymeric polydA-polydT have been conducted using UV-vis absorption titration studies, UV melting studies and circular dichroism spectroscopy. Competitive binding with the standard intercalator ethidium bromide and the minor groove binder 4',6-diamidino-2-phenylindole was monitored using fluorescence to identify the possible binding mode. Our results show that Cu(II)-NSAID complexes are highly sensitive to the subtle differences in backbone structures of polydA-dT and polydA-polydT and respond to them by exhibiting different binding properties, such as binding constants, effect on duplex stability and binding modes. Both complexes have a similar binding mode with polydA-dT, which is intercalative, but for polydA-polydT, the results point to a mixed mode of binding.