Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins
A series of new analogs of combretastatin A-4 (CA-4, 1) with the A or B-ring replaced by a 3-oxo-2,3-dihydrofurocoumarin or a furocoumarin residue have been designed and synthesized by employing a cross-coupling approach. All the compounds were evaluated for their cytotoxic activity with respect to...
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MDPI AG
2014-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/6/7881 |
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| author | Alla V. Lipeeva Elvira E. Shults Makhmut M. Shakirov Mikhail A. Pokrovsky Andrey G. Pokrovsky |
| author_facet | Alla V. Lipeeva Elvira E. Shults Makhmut M. Shakirov Mikhail A. Pokrovsky Andrey G. Pokrovsky |
| author_sort | Alla V. Lipeeva |
| collection | DOAJ |
| description | A series of new analogs of combretastatin A-4 (CA-4, 1) with the A or B-ring replaced by a 3-oxo-2,3-dihydrofurocoumarin or a furocoumarin residue have been designed and synthesized by employing a cross-coupling approach. All the compounds were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, MT-4, U-937) using conventional MTT assays. Structure-activity relationship analysis reveals that compounds 2, 3, 6–8 in which the (Z)-styryl substituent was connected to the 2-position of the 3-oxo-2,3-dihydrofurocoumarin core, demonstrated increased potency compared to 3-(Z)-styrylfurocoumarins 4, 5, 9–11. The methoxy-, hydroxyl- and formyl- substitution on the aromatic ring of the (Z)-styryl moiety seems to play an important role in this class of compounds. Compounds 2 and 3 showed the best potency against the CEM-13 cell lines, with CTD50 values ranging from 4.9 to 5.1 μM. In comparison with CA-4, all synthesized compounds presented moderate cytotoxic activity to the T-cellular human leucosis cells MT-4 and lymphoblastoid leukemia cells CEM-13, but most of them were active in the human monocyte cell lines U-937. |
| first_indexed | 2024-04-12T23:55:47Z |
| format | Article |
| id | doaj.art-736f4c3ab04d4fdcbb5142184ce2edef |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T23:55:47Z |
| publishDate | 2014-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-736f4c3ab04d4fdcbb5142184ce2edef2022-12-22T03:11:31ZengMDPI AGMolecules1420-30492014-06-011967881790010.3390/molecules19067881molecules19067881Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the CombretastatinsAlla V. Lipeeva0Elvira E. Shults1Makhmut M. Shakirov2Mikhail A. Pokrovsky3Andrey G. Pokrovsky4Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk 630090, RussiaLaboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk 630090, RussiaLaboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentjev Avenue 9, Novosibirsk 630090, RussiaMedicinal Department, Novosibirsk State University, Pirogova St. 2, Novosibirsk 630090, RussiaMedicinal Department, Novosibirsk State University, Pirogova St. 2, Novosibirsk 630090, RussiaA series of new analogs of combretastatin A-4 (CA-4, 1) with the A or B-ring replaced by a 3-oxo-2,3-dihydrofurocoumarin or a furocoumarin residue have been designed and synthesized by employing a cross-coupling approach. All the compounds were evaluated for their cytotoxic activity with respect to model cancer cell lines (CEM-13, MT-4, U-937) using conventional MTT assays. Structure-activity relationship analysis reveals that compounds 2, 3, 6–8 in which the (Z)-styryl substituent was connected to the 2-position of the 3-oxo-2,3-dihydrofurocoumarin core, demonstrated increased potency compared to 3-(Z)-styrylfurocoumarins 4, 5, 9–11. The methoxy-, hydroxyl- and formyl- substitution on the aromatic ring of the (Z)-styryl moiety seems to play an important role in this class of compounds. Compounds 2 and 3 showed the best potency against the CEM-13 cell lines, with CTD50 values ranging from 4.9 to 5.1 μM. In comparison with CA-4, all synthesized compounds presented moderate cytotoxic activity to the T-cellular human leucosis cells MT-4 and lymphoblastoid leukemia cells CEM-13, but most of them were active in the human monocyte cell lines U-937.http://www.mdpi.com/1420-3049/19/6/7881furocoumarinsoreoselonepsoralenSonogashira couplingsemi-hydrogenationcombretastatinscytotoxicity |
| spellingShingle | Alla V. Lipeeva Elvira E. Shults Makhmut M. Shakirov Mikhail A. Pokrovsky Andrey G. Pokrovsky Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins Molecules furocoumarins oreoselone psoralen Sonogashira coupling semi-hydrogenation combretastatins cytotoxicity |
| title | Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins |
| title_full | Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins |
| title_fullStr | Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins |
| title_full_unstemmed | Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins |
| title_short | Synthesis and Cytotoxic Activity of a New Group of Heterocyclic Analogues of the Combretastatins |
| title_sort | synthesis and cytotoxic activity of a new group of heterocyclic analogues of the combretastatins |
| topic | furocoumarins oreoselone psoralen Sonogashira coupling semi-hydrogenation combretastatins cytotoxicity |
| url | http://www.mdpi.com/1420-3049/19/6/7881 |
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