Synthesis and screening of Clerodane Diterpene analogues from 16 hydroxycleroda 3,13(14)-Zdien 15,16- olide for potential anti-mycobacterial activity

Abstract

Abstract In recent years, Clerodane diterpenes, a class of bioactive compounds, have come into the spotlight due to their amazing bioactivities. The "Indian Mast Tree" is a common name for a tall evergreen tree scientifically known as Polyalthia longifolia var. pendula. Three novel clerodane diterpene analogues were obtained by synthesizing 16-hydroxycleroda-3,13(14)-Zdien-15,16-olide (Lactone) with primary amines. Anti-tubercular activity was determined using Microplate Alamar Blue Assay. Among all the synthesised compounds from methanolic extract of seeds, results clearly showed that compounds 3 and 5 have significant anti tb activity with an MIC of 1.56 µg/ml against the Mycobacterium tuberculosis MTB H37Rv bacilli strain than the gold standard drugs pyrazinamide (3.125 µg/ml), ciprofloxacin (3.125 µg/ml), streptomycin (6.25 µg/ml) and rifampicin (6.25 µg/ml). Antimicrobial activity was also carried out by agar well diffusion method and its minimum inhibitory concentrations (MIC) were determined against Gram + ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) bacteria. Compound 5 exhibited significant antibacterial activity with Zone of inhibition of 10.8 mm with Gram + ve and 7.95 mm with Gram -ve bacteria at a conc of 50 µg/ml respectively. Furthermore, Compound 5 showed MIC at 5 µg/ml with both the bacterial strains. While tested for anti-fungal activity, Compound 5 showed Zone of inhibition of 10.8mm at conc. of 50 µg/ml. In the current investigation, three novel heterocycles (compounds 3–5) of the diterpenoid (compound 1) were prepared, in high yield, using one-pot, efficient approach. Further studies on in vivo, cytotoxic tests, mechanism of action and synthesis of a series of lactones will be used to determine the structural activity relationship of bioactive diterpenoid 1.