Naturally Occurring Anti-TB Agents: Isolation, Chemical Transformations and In Vitro Antitubercular Activities of Secondary Metabolites of Rhizomes of Alpinia galanga

Abstract

!A bioactivity-guided chemical examination of the acetone extract of the rhizomes of Alpinia galanga led to the isolation of six secondary metabolites, eucalyptol derivative (1) and phenylpropanoids (2-6). The structures of all of the isolated compounds (1-6) were elucidated on the basis of their spectral data. The isolated compounds (1-6) were in vitro assayed against active and dormant phenotypes of Mycobacterium tuberculosis H37Ra, respectively. Interestingly, 1′S-1′-acetoxychavicol acetate (2) showed good antitubercular activities against both active and dormant phenotypes of M. tuberculosis with IC 50 values of 1.04 µM and 2.69 µM, respectively. Tsuji-Trost and homodimerization reactions of the active compound (2) respectively resulted in the formation of two analogues, 7 and 8. Both of these synthesized analogues were also found to be active in vitro against active [IC 50 s of 3.24 and 3.87 µM, respectively, for compounds 7 and 8] and dormant [IC 50 s of 8.33 and 2.41 µM, respectively, for compounds 7 and 8] phenotypes of M. tuberculosis H37Ra, respectively. Key wordsAlpinia galanga · Zingiberaceae · phenyl propanoids · natural products · antitubercular activity Supporting information available online at http://www.thieme-connect.de/products Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (MTB), is a leading cause of death worldwide. The World Health Organization (WHO) reported [1] that approximately 9 million people were infected with TB globally in the year 2013 alone, which resulted in 1.5 million deaths, out of which an estimated 360 000 were infected with both human immunodeficiency virus (HIV) as well as tuberculosis. It is estimated that more than half of the TB-infected population is from Southeast Asia and Western Pacific Regions with China and India alone accounting for 11 % and 24 % of total cases, respectively. The treatment requires long spells due to which several patients discontinue the treatment in between, which results in the development of multidrug resistance (MDR) and extensively drug-resistant (XDR) TB. Both of these forms of TB are highly fatal, and the treatment is both expensive and complicated, thereby further complicating the prevention, control, and treatment of TB [2][3][4]. Although, at present, isoniazid, ethambutol, pyrazinamide, and rifampicin are available as effective anti-TB drugs, the threat posed by the development of multidrug resistance tuberculosis (MDR-TB) against the first-line as well as the second-line drugs is a serious issue [5,6]. Hence, the need for the development of new naturally occurring molecules to effectively treat TB and also address MDR and XDR assumes significance. The Zingiberaceae plant, Alpinia galanga (L.) Willd., is commonly known as galangal and is widely cultivated in China, India, and Southeast Asian countries such as Thailand, Indonesia, and the Philippines [7,8]. The rhizomes of this plant are extensively used as a spice or ginger substitute for flavoring foods. The rhizome has found several uses in...

Synthesis and anticancer studies of Michael adducts and Heck arylation products of sesquiterpene lactones, zaluzanin D and zaluzanin C from Vernonia arborea

“…Continuing our interest in naturally occurring sesquiterpene lactones 9 and other bioactive secondary metabolites, we wished to take up the chemical examination of V. arborea leaves for the isolation of bioactive secondary metabolites, zaluzanin C and zaluzanin D. In the present study, several structurally diverse Michael adducts of zaluzanin D have been synthesized with the formation of one or two new C–N bonds. Analogs of zaluzanin D with a new C–C bond formation have also been synthesized by using Pd catalyzed Heck coupling reaction.…”