Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30

Abstract

Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of Bengal, India, exhibited antimicrobial activity against human pathogenic bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive metabolite produced by the strain MB30 was purified through silica gel column chromatography and preparative HPLC. Purified metabolite was further characterized by FT-IR, LC-MS and NMR analyses. On the basis of spectroscopic data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP). The PPDHMP exhibited in vitro anticancer potential against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner with the IC50 concentration of 19.94 ± 1.23 and 16.73 ± 1.78 μg ml(-1) respectively. The acridine orange (AO)/ethidium bromide (EB) and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining of the IC50 concentration of PPDHMP-treated cancer cells exhibited an array of morphological changes such as nuclear condensation, cell shrinkage and formation of apoptotic bodies. The PPDHMP-treated cancer cells induced the progressive accumulation of fragmented DNA in a time-dependent manner. Based on the flow cytometric analysis, it has become evident that the compound was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of cyclin-D1, cyclin dependent kinase (CDK-2), anti-apoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL), activation of caspase-9 and 3 with the cleavage of PARP. The PPDHMP-treated cancer cells also showed the inhibition of migration and invasive capacity of cancer cells. In the present investigation, for the first time, we have reported the extraction, purification and characterization of an anticancer metabolite, PPDHMP from a new marine bacterium, Staphylococcus sp. strain MB30.

E-Liquid Containing a Mixture of Coconut, Vanilla, and Cookie Flavors Causes Cellular Senescence and Dysregulated Repair in Pulmonary Fibroblasts: Implications on Premature Aging

“…Pyrazines are associated with chocolate or roasted nut flavors. Pyrazines contain a heterocyclic motif that interacts with a diverse set of targets such as p53, the estrogen receptor, and the vascular endothelial growth factor (VEGF) making them an attractive target in the treatment of multiple diseases such as various cancers (Browne et al, 1991;Kamal et al, 2011;Lalitha et al, 2016). In hepatic stellate cells, tetramethylpyrazine induced senescence through a p53 dependent mechanism (Jin et al, 2017).…”

Evaluation of Antimicrobial, Enzyme Inhibitory, Antioxidant and Cytotoxic Activities of Partially Purified Volatile Metabolites of Marine Streptomyces sp.S2A

“…The first report on marine Staphylococcus sp. derived pyrrolo[1–a]pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl) was reported by Lalitha et al [ 36 ]. Purified metabolite was potentially active against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner.…”

The chemical composition, antifungal, antioxidant and antimutagenicity properties of bioactive compounds from fungal endophytes associated with Thai orchids

“…Barrero et al () also reported that gibepyrone A‐F exhibited potential antimicrobial activity. According to Lalitha, Veena, Vidhyapriya, Lakshmi, and Krishna (), pyrrolo [1,2‐a] pyrazine‐1,4‐dione, hexahydro‐3‐(2‐methylpropyl) inhibited cancer cell proliferation with an average IC 50 of 19.94 and 16.73 µg ml −1 against lung (A549) and cervical (HeLa) cancer cells, respectively. 2‐Coumaranone is a derivative of coumarin, an antioxidant compound, which has antioxidant properties (Revathi, Jeyaseelansenthinath, & Thirumalaikolundhusubramaian, ) and may play a role in the protection of the plant against oxidative stress (Torres et al, ).…”