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Issue 7, 2018
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Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity under estrogen-deficient conditions

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Abstract

β-Carbolines have been assessed for osteoclastogenesis. However, their effect on osteoblasts during estrogen deficiency is still unclear. Here, a series of novel piperazine and tetrazole tag β-carbolines have been synthesized and examined for osteoblast differentiation in vitro. In vitro data suggest that compound 8g is the most promising osteoblast differentiating agent that was evaluated for in vivo studies. Compound 8g promoted osteoblast mineralization, stimulated Runx2, BMP-2 and OCN expression levels, increased BrdU incorporation and inhibited generation of free radicals as well as nitric oxide. Since a piperazine group is involved in bone repair activity and β-carboline in IκB kinase (IKK) inhibition, compound 8g inhibited tumor necrosis factor α (TNFα) directed IκBα phosphorylation, preventing nuclear translocation of NF-κB thereby alleviating osteoblast apoptosis. In vivo studies show that compound 8g was able to restore estrogen deficiency-induced bone loss in ovariectomized rats without any toxicity, thus signifying its potential in bone-protection chemotherapy under postmenopausal conditions.

Graphical abstract: Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity under estrogen-deficient conditions

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Publication details

The article was received on 27 Feb 2018, accepted on 02 Jun 2018 and first published on 12 Jun 2018


Article type: Research Article
DOI: 10.1039/C8MD00109J
Citation: Med. Chem. Commun., 2018,9, 1213-1225
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    Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity under estrogen-deficient conditions

    A. Karvande, S. Khan, I. Khan, D. Singh, V. Khedgikar, P. Kushwaha, N. Ahmad, P. Kothari, A. Dhasmana, R. Kant, R. Trivedi and P. M. S. Chauhan, Med. Chem. Commun., 2018, 9, 1213
    DOI: 10.1039/C8MD00109J

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