Cinnamic Derivatives in Tuberculosis

Tuberculosis (TB) is a threat to worldwide public health, mainly caused by Mycobacterium tuberculosis (M.tb.) bacteria species. Despite the availability of effective treatment, tuberculosis is responsible for more than three million deaths annually worldwide. The high susceptibility of human immunodeficiency virus-infected persons to the disease (Nunn et al., 2005), the emergence of multi-drug-resistant (MDR-TB) strains (Rastogi et al., 1992, Kochi et al., 1993; Bloch et al., 1994) and extensively drug-resistant (XDR-TB) ones have brought this infectious disease into the focus of urgent scientific interest. For this reason, there is a growing need and urgency to discover new classes of chemical compounds acting with different mechanisms from those currently used. Cinnamic acid (1; Fig. 1) and derivatives have a century-old history as antituberculosis agents. For example, gradual improvement was observed when the TB-patients were treated with cinnamic acid (1) prepared from storax (Warbasse, 1894). Furthermore, in 1920s, ethylcinnamate (2) (Jacobson, 1919), sodium cinnamate (3) (Corper et al., 1920) and benzylcinnamate (4) (Gainsborough, 1928) were reported to be efficacious in the treatment of TB (Fig. 1). Nevertheless, we feel that this class of molecules remained underutilized until recent years. Particularly in the last two decades, there has been huge attention towards various natural and unnatural cinnamic derivatives and their antituberculosis efficacy. This chapter provides a comprehensive literature compilation concerning the synthesis so as the antituberculosis potency of various cinnamic acid, cinnamaldehyde and chalcone derivatives. We envisage that our effort in this chapter contributes a much needed and timely addition to the literature of medicinal research.