Aug 28, 2019

Bivalent furostene carbamates as antiproliferative and antiinflammatory agents

The Journal of Steroid Biochemistry and Molecular Biology
Nandini PathakArvind S Negi

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 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.

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Mentioned in this Paper

Chemical Bond
Carbamates
Caspase-3
Ring Dosage Form
TNF
Signaling (Initiator) Caspase Activity
Toxic Effect
Apoptosis
Cytokine
Inflammation

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