Gloriosine, a colchicine-like natural product, is widely
obtained
from
Gloriosa superba
roots. Despite
having remarkable anticancer potential, colchicine could not pave
its way to the clinic, while gloriosine is yet to be investigated
for its pharmacological effects. In the present work, 14 compounds,
including gloriosine, were isolated from the
G. superba
roots and were characterized by NMR spectroscopy. Gloriosine (
11
) was evaluated for its antiproliferative activity against
a panel of 15 human cancer cell lines of different tissues and normal
breast cells. Gloroisine (
11
) displayed significant antiproliferative
activity against various cancer cell lines selectively, with IC
50
values ranging from 32.61 to 100.28 nM. Further, gloriosine
(
11
) was investigated for its apoptosis-inducing ability
and found to form apoptotic bodies. It also inhibited A549 cell migration
in the wound healing assay. Finally, molecular docking studies were
performed to explore the possible binding modes of gloriosine with
the colchicine-binding site of tubulin protein. Our findings suggested
that gloriosine might be a potential lead for anticancer drug discovery.
The high probability (13%) of women developing breast cancer in their lifetimes in America is exacerbated by the emergence of multidrug resistance after exposure to first-line chemotherapeutic agents. Permeation glycoprotein (P-gp)-mediated drug efflux is widely recognized as the major driver of this resistance. Initial
in vitro
and
in vivo
investigations of the co-delivery of chemotherapeutic agents and P-gp inhibitors have yielded satisfactory results; however, these results have not translated to clinical settings. The systemic delivery of multiple agents causes adverse effects and drug–drug interactions, and diminishes patient compliance. Nanocarrier-based site-specific delivery has recently gained substantial attention among researchers for its promise in circumventing the pitfalls associated with conventional therapy. In this review article, we focus on nanocarrier-based co-delivery approaches encompassing a wide range of P-gp inhibitors along with chemotherapeutic agents. We discuss the contributions of active targeting and stimuli responsive systems in imparting site-specific cytotoxicity and reducing both the dose and adverse effects.
Ipomone (1), a novel diterpenoid along with seven
known compounds (2–8), was isolated
for the first time from the acidified hydroalcoholic extract of Ipomoea nil seeds. The structures of the isolated
compounds were elucidated via comprehensive NMR spectroscopic data.
The absolute configuration of 1 was ascertained through
NOESY, NMR, and ECD analyses. Compound 1 was found to
contain an unusual bicyclo-[3.2.1] octanone, which appeared first
time in any natural product that might be an artifact resulting from
the acid-catalyzed 1,2 alkyl shift/rearrangement. The novel compound
was screened for cytotoxic activity against a panel of 12 human cancer
cell lines and exhibited weak cytotoxicity with IC50 values
in the range of 34–86 μM (except for HEK-293 cells).
Microscopic studies revealed that compound 1 induced
apoptosis and autophagy in A549 cells. To further explore the signaling
pathway involved, immunoblot analysis was performed that confirmed
inhibition of apoptotic proteins PARP-1 and caspase-3 expression and
upregulation of LC3B expression by compound 1. The compound
was further subjected to molecular docking studies to evaluate its
binding affinity with p110α, PARP-1, and caspase-3 proteins.
and West Bengal produces major share of jackfruit in India (APAARI, 2012).The area under jackfruit cultivation in India is 1.85 lakh hectares with a production of 18.30 lakh MT. In Assam, the total area under jackfruit cultivation is estimated to be 22 thousand hectares with an annual production of 1.97 lakh MT (NHB, 2015-16).Jackfruit shows a considerable range of variations in morpho-agronomic characters
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