Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study
[Display omitted] •Compounds 8, 9 and 11 were the most active anticancer with IC50
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2021-02, Vol.31, p.115976-115976, Article 115976 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | El-Khouly, Omar A. Henen, Morkos A. El-Sayed, Magda A.-A. Shabaan, Mona I. El-Messery, Shahenda M. |
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•Compounds 8, 9 and 11 were the most active anticancer with IC50 |
| doi_str_mv | 10.1016/j.bmc.2020.115976 |
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•Compounds 8, 9 and 11 were the most active anticancer with IC50 < 10 µg/ml against 4 cell lines.•Compounds 8 and 9 showed very good inhibition activity of PI3K and computational study elucidate their activity.•Targeting MCF-7 cell line, compounds 8 and 9 induced apoptosis and showed cell cycle arrest at G2/M phase.•Antimicrobial activity of new compounds was assessed against Gram-positive, Gram-negative and fungi.•Antiquorum-sensing activity of new series was assessed using Chromobacterium violaceum.
A new series of benzofuran derivatives has been designed and synthesized. The structures of the synthesized compounds have been confirmed by the use of 1H NMR, 13C NMR, 2D 1H–1H NOESY NMR, and IR. Anticancer activity is evaluated against Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), Epitheliod carcinoma cervix cancer (Hela) and human prostate cancer (PC3). Compounds 8, 9, and 11 showed the highest activity towards the four cell lines with an IC50 range of 8.49–16.72 µM, 6.55–13.14 µM and 4–8.99 µM respectively in comparison to DOX (4.17–8.87 µM). Phosphatidylinositol-3-kinases (PI3K) inhibition was evaluated against the most active anticancer compounds 8, 9 and 11. Compounds 8, 9 and 11 showed good inhibitory activity against PI3Kα with IC50 values 4.1, 7.8, and 20.5 µM, respectively in comparison to 6.18 µM for the reference compound LY294002. In addition, activity of compounds 8 and 9 on cell cycle arrest and induction of apoptosis in different phases of MCF-7 cells were assessed and detected pre-G1 apoptosis and cell growth arrest at G2/M. Also, both extrinsic and intrinsic apoptosis in MCF-7 cells induced by compounds 8 and 9. Molecular docking, binding affinity surface mapping, and contact preference of the synthesized compounds 8, 9 and 11 against PI3K were estimated and studied computationally using molecular operating environment software (MOE) and showed good interaction with essential residues for inhibition Val851. In addition, antimicrobial activity was evaluated against gram positive isolates as Staphylococcus aureus and Bacillus cereus, gram negative isolate as Escherichia coli, Pseudomonas aeruginosa and antifungal potential against Candida albicans. Compound 17 showed outstanding anti Gram-positive activity with MIC values 8 and 256 µg/mL in Staphylococcus aureus and Bacillus cereus respectively. Also, compounds 15, 17, 18 and 21 showed good anti Gram-negative activity with MIC value 512 µg/mL for all compounds. In addition, the state-of-art quorum sensing (QS) inhibiting effects were detected using Chromobacterium violaceum and compounds 7, 9, 10, 11, and 12 showed good QS inhibition (3, 3, 5, 2, and 7 mm).</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2020.115976</identifier><identifier>PMID: 33388654</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anticancer ; Antimicrobial ; Benzofuran ; Hybridization ; Molecular modeling ; NOESY ; PI3K ; Quorum sensing</subject><ispartof>Bioorganic & medicinal chemistry, 2021-02, Vol.31, p.115976-115976, Article 115976</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-91b5bf767f96fd5f80187f7c188a49a54a426a9613493ae9d02d2dbd925ca7063</citedby><cites>FETCH-LOGICAL-c451t-91b5bf767f96fd5f80187f7c188a49a54a426a9613493ae9d02d2dbd925ca7063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2020.115976$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33388654$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Khouly, Omar A.</creatorcontrib><creatorcontrib>Henen, Morkos A.</creatorcontrib><creatorcontrib>El-Sayed, Magda A.-A.</creatorcontrib><creatorcontrib>Shabaan, Mona I.</creatorcontrib><creatorcontrib>El-Messery, Shahenda M.</creatorcontrib><title>Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
•Compounds 8, 9 and 11 were the most active anticancer with IC50 < 10 µg/ml against 4 cell lines.•Compounds 8 and 9 showed very good inhibition activity of PI3K and computational study elucidate their activity.•Targeting MCF-7 cell line, compounds 8 and 9 induced apoptosis and showed cell cycle arrest at G2/M phase.•Antimicrobial activity of new compounds was assessed against Gram-positive, Gram-negative and fungi.•Antiquorum-sensing activity of new series was assessed using Chromobacterium violaceum.
A new series of benzofuran derivatives has been designed and synthesized. The structures of the synthesized compounds have been confirmed by the use of 1H NMR, 13C NMR, 2D 1H–1H NOESY NMR, and IR. Anticancer activity is evaluated against Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), Epitheliod carcinoma cervix cancer (Hela) and human prostate cancer (PC3). Compounds 8, 9, and 11 showed the highest activity towards the four cell lines with an IC50 range of 8.49–16.72 µM, 6.55–13.14 µM and 4–8.99 µM respectively in comparison to DOX (4.17–8.87 µM). Phosphatidylinositol-3-kinases (PI3K) inhibition was evaluated against the most active anticancer compounds 8, 9 and 11. Compounds 8, 9 and 11 showed good inhibitory activity against PI3Kα with IC50 values 4.1, 7.8, and 20.5 µM, respectively in comparison to 6.18 µM for the reference compound LY294002. In addition, activity of compounds 8 and 9 on cell cycle arrest and induction of apoptosis in different phases of MCF-7 cells were assessed and detected pre-G1 apoptosis and cell growth arrest at G2/M. Also, both extrinsic and intrinsic apoptosis in MCF-7 cells induced by compounds 8 and 9. Molecular docking, binding affinity surface mapping, and contact preference of the synthesized compounds 8, 9 and 11 against PI3K were estimated and studied computationally using molecular operating environment software (MOE) and showed good interaction with essential residues for inhibition Val851. In addition, antimicrobial activity was evaluated against gram positive isolates as Staphylococcus aureus and Bacillus cereus, gram negative isolate as Escherichia coli, Pseudomonas aeruginosa and antifungal potential against Candida albicans. Compound 17 showed outstanding anti Gram-positive activity with MIC values 8 and 256 µg/mL in Staphylococcus aureus and Bacillus cereus respectively. Also, compounds 15, 17, 18 and 21 showed good anti Gram-negative activity with MIC value 512 µg/mL for all compounds. In addition, the state-of-art quorum sensing (QS) inhibiting effects were detected using Chromobacterium violaceum and compounds 7, 9, 10, 11, and 12 showed good QS inhibition (3, 3, 5, 2, and 7 mm).</description><subject>Anticancer</subject><subject>Antimicrobial</subject><subject>Benzofuran</subject><subject>Hybridization</subject><subject>Molecular modeling</subject><subject>NOESY</subject><subject>PI3K</subject><subject>Quorum sensing</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc9u1DAQxi0EotvCA3BBPnJoFjtxnBikSqjiT0UlkICzNbEnXa8Su7WToOU5-sB4u6WCCyfP2N98Y30_Ql5wtuaMy9fbdTeadcnK3PNaNfIRWXEhRVFVij8mK6ZkW7BWySNynNKWMVYKxZ-So6qq2lbWYkVuv-38tMHk0ikFPzkD3mDMpb1rR2di6BwMFBcYZphc8DT01ONP2qH_Ffo5gqcdJLTUYnRLliyY3tCvF9Vn6vzGdW4_dEpv5hDnkSb0yfmruw1jGNDMA8RcWRz212ma7e4ZedLDkPD5_XlCfnx4__38U3H55ePF-bvLwoiaT4XiXd31jWx6JXtb9y3jbdM3hrctCAW1AFFKUJJXQlWAyrLSlrazqqwNNExWJ-Ts4Hs9dyNag36KMOjr6EaIOx3A6X9fvNvoq7DoRuXM2yYbvLo3iOFmxjTp0SWDwwAew5x0KZo662quspQfpDnQlCL2D2s403uaeqszTb2nqQ8088zLv__3MPEHXxa8PQgwp7Q4jDoZh5mgdRHNpG1w_7H_DQAktD4</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>El-Khouly, Omar A.</creator><creator>Henen, Morkos A.</creator><creator>El-Sayed, Magda A.-A.</creator><creator>Shabaan, Mona I.</creator><creator>El-Messery, Shahenda M.</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210201</creationdate><title>Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study</title><author>El-Khouly, Omar A. ; Henen, Morkos A. ; El-Sayed, Magda A.-A. ; Shabaan, Mona I. ; El-Messery, Shahenda M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-91b5bf767f96fd5f80187f7c188a49a54a426a9613493ae9d02d2dbd925ca7063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anticancer</topic><topic>Antimicrobial</topic><topic>Benzofuran</topic><topic>Hybridization</topic><topic>Molecular modeling</topic><topic>NOESY</topic><topic>PI3K</topic><topic>Quorum sensing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-Khouly, Omar A.</creatorcontrib><creatorcontrib>Henen, Morkos A.</creatorcontrib><creatorcontrib>El-Sayed, Magda A.-A.</creatorcontrib><creatorcontrib>Shabaan, Mona I.</creatorcontrib><creatorcontrib>El-Messery, Shahenda M.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Khouly, Omar A.</au><au>Henen, Morkos A.</au><au>El-Sayed, Magda A.-A.</au><au>Shabaan, Mona I.</au><au>El-Messery, Shahenda M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>31</volume><spage>115976</spage><epage>115976</epage><pages>115976-115976</pages><artnum>115976</artnum><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
•Compounds 8, 9 and 11 were the most active anticancer with IC50 < 10 µg/ml against 4 cell lines.•Compounds 8 and 9 showed very good inhibition activity of PI3K and computational study elucidate their activity.•Targeting MCF-7 cell line, compounds 8 and 9 induced apoptosis and showed cell cycle arrest at G2/M phase.•Antimicrobial activity of new compounds was assessed against Gram-positive, Gram-negative and fungi.•Antiquorum-sensing activity of new series was assessed using Chromobacterium violaceum.
A new series of benzofuran derivatives has been designed and synthesized. The structures of the synthesized compounds have been confirmed by the use of 1H NMR, 13C NMR, 2D 1H–1H NOESY NMR, and IR. Anticancer activity is evaluated against Hepatocellular carcinoma (HePG2), mammary gland breast cancer (MCF-7), Epitheliod carcinoma cervix cancer (Hela) and human prostate cancer (PC3). Compounds 8, 9, and 11 showed the highest activity towards the four cell lines with an IC50 range of 8.49–16.72 µM, 6.55–13.14 µM and 4–8.99 µM respectively in comparison to DOX (4.17–8.87 µM). Phosphatidylinositol-3-kinases (PI3K) inhibition was evaluated against the most active anticancer compounds 8, 9 and 11. Compounds 8, 9 and 11 showed good inhibitory activity against PI3Kα with IC50 values 4.1, 7.8, and 20.5 µM, respectively in comparison to 6.18 µM for the reference compound LY294002. In addition, activity of compounds 8 and 9 on cell cycle arrest and induction of apoptosis in different phases of MCF-7 cells were assessed and detected pre-G1 apoptosis and cell growth arrest at G2/M. Also, both extrinsic and intrinsic apoptosis in MCF-7 cells induced by compounds 8 and 9. Molecular docking, binding affinity surface mapping, and contact preference of the synthesized compounds 8, 9 and 11 against PI3K were estimated and studied computationally using molecular operating environment software (MOE) and showed good interaction with essential residues for inhibition Val851. In addition, antimicrobial activity was evaluated against gram positive isolates as Staphylococcus aureus and Bacillus cereus, gram negative isolate as Escherichia coli, Pseudomonas aeruginosa and antifungal potential against Candida albicans. Compound 17 showed outstanding anti Gram-positive activity with MIC values 8 and 256 µg/mL in Staphylococcus aureus and Bacillus cereus respectively. Also, compounds 15, 17, 18 and 21 showed good anti Gram-negative activity with MIC value 512 µg/mL for all compounds. In addition, the state-of-art quorum sensing (QS) inhibiting effects were detected using Chromobacterium violaceum and compounds 7, 9, 10, 11, and 12 showed good QS inhibition (3, 3, 5, 2, and 7 mm).</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33388654</pmid><doi>10.1016/j.bmc.2020.115976</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elsevier ScienceDirect Journals Complete |
| subjects | Anticancer Antimicrobial Benzofuran Hybridization Molecular modeling NOESY PI3K Quorum sensing |
| title | Synthesis, anticancer and antimicrobial evaluation of new benzofuran based derivatives: PI3K inhibition, quorum sensing and molecular modeling study |
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