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.
Multicomponent self-assembly of Mn
2
(CO)
10
, a bis-chelating aminoquinonato (ON∩ON)
bridge (L), and an
ester/amide-functionalized flexible neutral ditopic linker (L′)
has resulted into the formation of M
2
LL′-type manganese(I)-based
dinuclear metallastirrups of general formula [{(CO)
3
Mn(μ-η
4
-L)Mn(CO)
3
}(μ-L′)] (
1
–
10
). Compounds
1
–
10
were accomplished via orthogonal bonding of the aminoquinone ligand
(2,5-bis(
n
-butylamino)-1,4-benzoquinone/2,5-bis(phenethylamino)-1,4-benzoquinone)
and ditopic pyridyl ligand to manganese carbonyl. The resultant metallastirrups
were characterized using elemental analyses and IR, UV–vis,
1
H NMR, and electrospray ionization-mass spectroscopic techniques.
The molecular structure of
6
was confirmed by single-crystal
X-ray diffraction methods. Furthermore, molecular recognition capabilities
of
1
,
5
,
7
, and
9
were evaluated with aromatic compounds containing hydroxy/amine
functionalities. Anticancer activities of compounds
1
−
3
,
5
−
7
,
9
, and
10
were investigated against three cancer
cell lines, that is, lung (A549), colon (HCT-15), and cervical (HeLa)
as well as on normal cells (HEK 293). Compound
9
showed
a broad-spectrum inhibition toward these cancer cells upon exposure
to visible light. The myoglobin assay was performed using UV–vis
absorption spectroscopy to investigate the visible-light-triggered
CO release from
5
and
9
that could be related
to their ability to effectively inhibit cancer cells. In addition,
morphological studies confirmed the induction of autophagy due to
the treatment of cancer cells using compound
9
.
Selenolato-bridged
manganese(I)-based dinuclear metallacycles [{(CO)3Mn(μ-SeC6H5)2Mn(CO)3}(μ-L)]
(1–4) were achieved in a
single-step process by the self-assembly of dimanganese decacarbonyl,
diphenyl diselenide, and flexible ditopic ester-functionalized pyridyl
ligands [1, L = o-phenylene diisonicotinate
(pdi); 2, L = 1,6-hexanediyl di-4-pyridine carboxylate
(hdp); 3, L = 4-pyridine carboxylic acid diethylene glycol
diester (pcadgd); 4, L = 4-pyridine carboxylic acid triethylene
glycol diester (pcatgd)]. Synthesis of a series of selenolato-bridged
dinuclear Mn(I)-based metallacycles was facilitated via oxidative
addition of C6H5Se–SeC6H5 to (CO)5Mn–Mn(CO)5 with simultaneous
coordination of flexible ditopic pyridyl linkers in an orthogonal
fashion. The metallacycles were characterized by IR, UV–vis,
NMR, and electrospray ionization-mass spectroscopic techniques and
elemental analysis. Solid-state structural elucidation of 3 was carried out using single-crystal X-ray diffraction methods.
In addition, anticancer activity studies were carried out for compounds 2–4 with various cancer cell lines. Furthermore, compound 3 was probed to evaluate its potential CO-releasing property
using myoglobin assay.
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