Bivalent furostene carbamates as antiproliferative and antiinflammatory agents

Article abstract of DOI:10.1016/j.jsbmb.2019.105457

Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.

Full text of DOI:10.1016/j.jsbmb.2019.105457

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Bivalent furostene carbamates as antiproliferative and antiinflammatory
agents
Nandini Pathak, Kaneez Fatima, Sneha Singh, Divya Mishra, Amit
Chand Gupta, Yogesh Kumar, Debabrata Chanda, D.U. Bawankule,
Karuna Shanker, Feroz Khan, Atul Gupta, Suaib Luqman, Arvind S.
Negi
PII:
S0960-0760(19)30252-3
https://doi.org/10.1016/j.jsbmb.2019.105457
105457
DOI:
Article Number:
Reference:
SBMB 105457
To appear in:
Journal of Steroid Biochemistry & Molecular Biology
Received Date:
Revised Date:
Accepted Date:
2 May 2019
20 August 2019
23 August 2019
Please cite this article as: Pathak N, Fatima K, Singh S, Mishra D, Gupta AC, Kumar Y,
Chanda D, Bawankule DU, Shanker K, Khan F, Gupta A, Luqman S, Negi AS, Bivalent
furostene carbamates as antiproliferative and antiinflammatory agents, Journal of Steroid
Biochemistry and Molecular Biology (2019), doi: https://doi.org/10.1016/j.jsbmb.2019.105457

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Bivalent furostene carbamates as antiproliferative and antiinflammatory agents
Nandini Pathak,a# Kaneez Fatima,a,b# Sneha Singh,a Divya Mishra,a Amit Chand Gupta,a Yogesh Kumar,a Debabrata
Chanda,a,b D.U. Bawankule,a,b Karuna Shanker,a,b Feroz Khan,a,b Atul Gupta,a,b Suaib Luqman,*a,b Arvind S. Negi* a,b
aCSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), P.O. CIMAP, Kukrail Picnic Spot Road, Lucknow-
226 015, Uttar Pradesh, India.
bAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, Uttar Pradesh, India.
#Equal authorship
* Corresponding Authors: arvindcimap@rediffmail.com (AS Negi); s.luqman@cimap.res.in (S. Luqman) ;
Tel: +91-522- 2718583; Fax: +91-522-2342666; CIMAP Communication No. CIMAP/PUB/2019/May/26.
Graphical abstract
Diosgenin
Sapogenin
Dioscorea floribunda
(Rhizomes)
Dioscin
Saponin
Anticancer
-MDA-MB-231 (IC50):13.5M
-G1 Phase arrest &
apoptosis induction
N
O
N
O
O
-Reduction of EAC (65.4%) &
safe up to 300 mg/kg oral dose
O
Furostene carbamate 10
Antiinflammatory
-Inhibition TNF- (33.7% ) &
IL-6 (49.1%)
O
Carbamate derivative at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin exhibits potent
anticancer activity against breast Cancer.
Highlights

C26-furostene carbamates have been prepared from
1
Diosgenin

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.

Carbamate 10, novel, antiproliferative against triple negative
breast cancer (IC50=13.5 µM) induces apoptosis by activation of caspase cascade pathway.



Concomitant antiproliferative and antiinflammatory property
as well is important.
75 mg/kg dose
Efficacy: In-vivo anticancer activity 65.4% tumour reduction at
Safety: in-vivo acute toxicity- safe up to 300mg/kg dose.
Abstract
Breast cancer is the most prevalent cancer in women affecting about 12% of world’s female population. It is a
multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative
agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring)
of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by
arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was
observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited
moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced
inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites
carcinoma significantly in mice. It was well tolerated and safe up in acute oral toxicity in Swiss albino mice. The
concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be
optimized for a better anti-breast cancer candidate.
Keywords: Dioscorea floribunda, anticancer, apoptosis, caspase, Ehrlich ascites carcinoma, acute oral
toxicity
Abbreviations: APCI-TOF-MS, Atmospheric Pressure Chemical Ionisation-Time of Flight Mass Spectrometry;
CDCl3, Deuterated chloroform; DMAP, Dimethylaminopyridine; ESI-MS, Electrospray Mass Ionisation-Mass
Spectrometry; EAC, Ehrlich Ascites Carcinoma; HRMS, High Resolution Mass Spectrometry; HER 2, Human
Epidermal growth factor Receptor 2; IL-6, Interleukin 6; IAEC, Institutional Animal Ethical Committee; LPS,
Lipopolysaccharide; LC-MS, Liquid Chromatography-Mass Spectrometry; MeOH, Methanol; RT, Room
Temperature; SI, Selectivity Index; TNF, Tumour Necrosis Factor; UPLC, Ultra Performance Liquid
Chromatography
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