Benzofuran-pyran hybrids: A new class of potential bone anabolic agents. Issue 10 (1st June 2018)

• Record Type: Journal Article
• Authors: Gupta, Sampa; Adhikary, Sulekha; Modukuri, Ram K.; Choudhary, Dharmendra; Trivedi, Ritu; Sashidhara, Koneni V.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 10(2018)
• Page Start: 1719
• Page End: 1724
• Publication Date: 2018-06-01
• Subjects: Benzofuran-pyran hybrids -- Bone anabolic agents -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.04.041
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: New benzofuran-pyran hybrids were synthesised. Compounds 22 and 24 were found potent in ALP activity. Compounds 22 and 34 were active in enhancing mineralization in osteoblast cells. Compound 22 up-regulated the expression of osteogenic genes. Abstract: Benzofuran moiety is an important pharmacophore showing positive effects on bone health. In the present study, sixteen benzofuran-pyran hybrids were synthesized and were evaluated for their osteogenic effects on primary osteoblast cells isolated from calvaria. Compounds 22 and 24 were found potent in stimulating osteoblast differentiation as assessed by the alkaline phosphatase activity. These compounds were also found to be nontoxic to osteoblast cells as compared to the control cells in MTT assay. Further, Alizarin Red-S staining for visualization of calcium nodules demonstrated compounds 22 and 34 as active in enhancing mineralization in osteoblast cells. Additionally, transcriptional analysis of these compounds on osteoblast cells revealed that compound 22 up-regulated the expression of osteogenic genes RUNX2, BMP-2, COL-1, thus substantiating that compound 22 having two geminal methyl groups in its R 3 position is a potent osteogenic agent. Additionally, compound 22 enhanced the ability of bone marrow stromal cells to differentiate towards osteoblast lineage and therefore can be further studied in vivo in bone loss model.