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Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity in estrogen-deficient condition

Abstract

β-carbolines have been assessed in osteoclastogenesis. However, their effect on osteoblast during estrogen deficiency is still unclear. Here, a series of novel piperazine and tetrazole tag β-carbolines has 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 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 IҡBα phosphorylation; preventing nuclear translocation of NF-ҡB thereby alleviated 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 in postmenopausal condition.

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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, Accepted Manuscript
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    Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity in estrogen-deficient condition

    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, Accepted Manuscript , DOI: 10.1039/C8MD00109J

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