Benzofuran-pyran hybrids: A new class of potential bone anabolic agents
[Display omitted] •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. Benzofuran moiety is an important pha...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2018-06, Vol.28 (10), p.1719-1724 |
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| creator | Gupta, Sampa Adhikary, Sulekha Modukuri, Ram K. Choudhary, Dharmendra Trivedi, Ritu Sashidhara, Koneni V. |
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•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.
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 R3 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. |
| doi_str_mv | 10.1016/j.bmcl.2018.04.041 |
| format | Article |
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•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.
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 R3 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.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2018.04.041</identifier><identifier>PMID: 29703629</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anabolic Agents - chemical synthesis ; Anabolic Agents - chemistry ; Anabolic Agents - pharmacology ; Benzofuran-pyran hybrids ; Benzofurans - chemistry ; Benzofurans - pharmacology ; Bone anabolic agents ; Bone and Bones - drug effects ; Bone Density - drug effects ; Cell Differentiation - drug effects ; Cell Survival - drug effects ; Dose-Response Relationship, Drug ; Humans ; Mesenchymal Stem Cells - cytology ; Molecular Structure ; Osteoblasts - cytology ; Osteoblasts - drug effects ; Osteogenesis - drug effects ; Osteogenesis - genetics ; Pyrans - chemistry ; Pyrans - pharmacology ; RNA, Messenger - drug effects ; RNA, Messenger - genetics ; Structure-Activity Relationship ; Synthesis</subject><ispartof>Bioorganic & medicinal chemistry letters, 2018-06, Vol.28 (10), p.1719-1724</ispartof><rights>2018 Elsevier Ltd</rights><rights>Copyright © 2018 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-19667d33e2412fb3d46a62af72661fa2aae9fb7e0cdde22192aa6706611052e93</citedby><cites>FETCH-LOGICAL-c356t-19667d33e2412fb3d46a62af72661fa2aae9fb7e0cdde22192aa6706611052e93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2018.04.041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29703629$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Sampa</creatorcontrib><creatorcontrib>Adhikary, Sulekha</creatorcontrib><creatorcontrib>Modukuri, Ram K.</creatorcontrib><creatorcontrib>Choudhary, Dharmendra</creatorcontrib><creatorcontrib>Trivedi, Ritu</creatorcontrib><creatorcontrib>Sashidhara, Koneni V.</creatorcontrib><title>Benzofuran-pyran hybrids: A new class of potential bone anabolic agents</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
•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.
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 R3 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.</description><subject>Anabolic Agents - chemical synthesis</subject><subject>Anabolic Agents - chemistry</subject><subject>Anabolic Agents - pharmacology</subject><subject>Benzofuran-pyran hybrids</subject><subject>Benzofurans - chemistry</subject><subject>Benzofurans - pharmacology</subject><subject>Bone anabolic agents</subject><subject>Bone and Bones - drug effects</subject><subject>Bone Density - drug effects</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Molecular Structure</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - drug effects</subject><subject>Osteogenesis - drug effects</subject><subject>Osteogenesis - genetics</subject><subject>Pyrans - chemistry</subject><subject>Pyrans - pharmacology</subject><subject>RNA, Messenger - drug effects</subject><subject>RNA, Messenger - genetics</subject><subject>Structure-Activity Relationship</subject><subject>Synthesis</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UE1LAzEUDKLYWv0DHiRHL1tfPprtipdatAoFLwreQjb7VlO2m5pslfrrTWn1KAzvwbyZgTeEnDMYMmDqajEsl7YZcmDjIcgEdkD6TCqZCQmjQ9KHQkE2LuRrj5zEuABgEqQ8Jj1e5CAUL_pkdovtt6_XwbTZapMmfd-UwVXxmk5oi1_UNiZG6mu68h22nTMNLX2L1LSm9I2z1LwlOp6So9o0Ec_2e0Be7u-epw_Z_Gn2OJ3MMytGqstYoVReCYFcMl6XopLKKG7qnCvFasONwaIucwRbVcg5KxKjckhHBiOOhRiQy13uKviPNcZOL1202DSmRb-OmoPgEriArZTvpDb4GAPWehXc0oSNZqC3BeqF3haotwVqkAksmS72-etyidWf5bexJLjZCTB9-ekw6GgdthYrF9B2uvLuv_wfrPyAxg</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Gupta, Sampa</creator><creator>Adhikary, Sulekha</creator><creator>Modukuri, Ram K.</creator><creator>Choudhary, Dharmendra</creator><creator>Trivedi, Ritu</creator><creator>Sashidhara, Koneni V.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20180601</creationdate><title>Benzofuran-pyran hybrids: A new class of potential bone anabolic agents</title><author>Gupta, Sampa ; Adhikary, Sulekha ; Modukuri, Ram K. ; Choudhary, Dharmendra ; Trivedi, Ritu ; Sashidhara, Koneni V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-19667d33e2412fb3d46a62af72661fa2aae9fb7e0cdde22192aa6706611052e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Anabolic Agents - chemical synthesis</topic><topic>Anabolic Agents - chemistry</topic><topic>Anabolic Agents - pharmacology</topic><topic>Benzofuran-pyran hybrids</topic><topic>Benzofurans - chemistry</topic><topic>Benzofurans - pharmacology</topic><topic>Bone anabolic agents</topic><topic>Bone and Bones - drug effects</topic><topic>Bone Density - drug effects</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Molecular Structure</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - drug effects</topic><topic>Osteogenesis - drug effects</topic><topic>Osteogenesis - genetics</topic><topic>Pyrans - chemistry</topic><topic>Pyrans - pharmacology</topic><topic>RNA, Messenger - drug effects</topic><topic>RNA, Messenger - genetics</topic><topic>Structure-Activity Relationship</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gupta, Sampa</creatorcontrib><creatorcontrib>Adhikary, Sulekha</creatorcontrib><creatorcontrib>Modukuri, Ram K.</creatorcontrib><creatorcontrib>Choudhary, Dharmendra</creatorcontrib><creatorcontrib>Trivedi, Ritu</creatorcontrib><creatorcontrib>Sashidhara, Koneni V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gupta, Sampa</au><au>Adhikary, Sulekha</au><au>Modukuri, Ram K.</au><au>Choudhary, Dharmendra</au><au>Trivedi, Ritu</au><au>Sashidhara, Koneni V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Benzofuran-pyran hybrids: A new class of potential bone anabolic agents</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>28</volume><issue>10</issue><spage>1719</spage><epage>1724</epage><pages>1719-1724</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
•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.
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 R3 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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29703629</pmid><doi>10.1016/j.bmcl.2018.04.041</doi><tpages>6</tpages></addata></record> |
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| subjects | Anabolic Agents - chemical synthesis Anabolic Agents - chemistry Anabolic Agents - pharmacology Benzofuran-pyran hybrids Benzofurans - chemistry Benzofurans - pharmacology Bone anabolic agents Bone and Bones - drug effects Bone Density - drug effects Cell Differentiation - drug effects Cell Survival - drug effects Dose-Response Relationship, Drug Humans Mesenchymal Stem Cells - cytology Molecular Structure Osteoblasts - cytology Osteoblasts - drug effects Osteogenesis - drug effects Osteogenesis - genetics Pyrans - chemistry Pyrans - pharmacology RNA, Messenger - drug effects RNA, Messenger - genetics Structure-Activity Relationship Synthesis |
| title | Benzofuran-pyran hybrids: A new class of potential bone anabolic agents |
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