Publication:
Tail-Approach-Based Design and Synthesis of Coumarin-Monoterpenes as Carbonic Anhydrase Inhibitors and Anticancer Agents

Simple item page
dc.contributor.authorKurt B. Z.
dc.contributor.authorCelebi G.
dc.contributor.authorÖztürk Civelek D.
dc.contributor.authorAngeli A.
dc.contributor.authorAkdemir A.
dc.contributor.authorSonmez F.
dc.contributor.authorSupuran C. T.
dc.contributor.institutionauthorÖZTÜRK CİVELEK, DİLEK
dc.contributor.institutionauthorAKDEMİR, ATİLLA
dc.contributor.institutionauthorZENGİN KURT, BELMA
dc.date.accessioned2023-02-08T21:30:15Z
dc.date.available2023-02-08T21:30:15Z
dc.date.issued2023-02-01
dc.description.abstractIn this study, sixty novel coumarin-monoterpene compounds were synthesized in two series [thirty-two compounds (12-43) bearing a triazole ring in the first series, and twenty-eight compounds (44-71) bearing an alkyl chain in the second one]. Their inhibitory effects on the human carbonic anhydrase (hCA) isoforms I, II, IX, and XII and anticancer potentials were determined. All synthesized molecules selectively inhibited CA IX and XII. 23 and 42 were found to be the strongest inhibitors, with K i values of 1.9 nM against hCA IX. Also, 70 showed the highest inhibitory activity with a K i value of 4.9 nM against hCA XII. Moreover, their cytotoxic effects on colon adenocarcinoma (HT-29), prostate adenocarcinoma (PC-3), and breast adenocarcinoma (MCF-7) cell lines were evaluated. According to the cytotoxicity results, 14 (IC50 = 2.48 μM) and 63 (IC50 = 3.91 μM) exhibited the highest cytotoxicity on the MCF-7 cells, while 23 showed the strongest cytotoxic effect on both PC-3 (IC50 = 9.40 μM) and HT-29 (IC50 = 12.10 μM) cell lines. 14, 23, and 66 decreased CA IX and CA XII protein expression in HT-29 cells, while 23 and 66 showed the strongest reduction of both CA IX and CA XII in MCF-7 cells. All of the selected compounds increased total apoptosis in a concentration-dependent manner in HT-29 and MCF-7 cells. 14 has the strongest apoptotic effect in MCF-7 cells. 23 increased early apoptosis primarily, while 14 and 66 increased total apoptosis in HT-29. In addition, PI/Hoechst staining proves that apoptotic cells are increased in HT-29 with an effect of 14, 23, and 66. As a result of the modeling studies, it has been shown that only the open coumarin form of the compounds can interact directly with the active-site Zn2+ ion. It has been shown that coumarin-monoterpene structures with different alkyl and monoterpene groups both specifically inhibit CA IX and XII and exhibit specific cytotoxicity in different cell lines.
dc.identifier.citationKurt B. Z., Celebi G., Öztürk Civelek D., Angeli A., Akdemir A., Sonmez F., Supuran C. T., "Tail-Approach-Based Design and Synthesis of Coumarin-Monoterpenes as Carbonic Anhydrase Inhibitors and Anticancer Agents", ACS OMEGA, 2023
dc.identifier.doi10.1021/acsomega.2c07459
dc.identifier.issn2470-1343
dc.identifier.pubmed36816648
dc.identifier.scopus85147567058
dc.identifier.urihttps://hdl.handle.net/20.500.12645/35175
dc.identifier.wosWOS:000932420200001
dc.relation.ispartofACS OMEGA
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleTail-Approach-Based Design and Synthesis of Coumarin-Monoterpenes as Carbonic Anhydrase Inhibitors and Anticancer Agents
dc.typearticle
dspace.entity.typePublication
local.avesis.id1328f2b2-a3c9-4db4-9538-06f0176fca99
relation.isAuthorOfPublication821c461c-752b-4a78-a2e5-a6aaf5076b88
relation.isAuthorOfPublication19bc513a-c695-4e72-ba1d-83b8d6c574c8
relation.isAuthorOfPublication3fd265b5-fdd8-4c56-949b-deb0303c3db7
relation.isAuthorOfPublication.latestForDiscovery821c461c-752b-4a78-a2e5-a6aaf5076b88
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
zengin-kurt-et-al-2023-tail-approach-based-design-and-synthesis-of-coumarin-monoterpenes-as-carbonic-anhydrase.pdf
Size:
14.02 MB
Format:
Adobe Portable Document Format
Download
Collections
Yayınlar - Eserler