Хетероциклени аналози на комбретастатин А-4 Синтез и биологична активност : Автореферат
The general objective of this research is the synthesis of novel heterocyclic analogues of combretastatin A-4 - natural cis-stilbene with very promising anticancer activity. The target compounds contain methoxystyryl fragment introduced in different position of benzoxazolone or benzothiazolone ring....
| Основен автор: | Герова, Мариана Стефанова 1978- |
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| Други автори: | Петров, Огнян Иванов 1965- (научен ръководител), Gerova, Mariana Stefanova 1978- |
| Формат: | Книга |
| Език: | Bulgarian |
| Публикувано: |
София
2012
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| Предмети: | |
| Онлайн достъп: |
Пълен текст |
| Резюме: |
The general objective of this research is the synthesis of novel heterocyclic analogues of combretastatin A-4 - natural cis-stilbene with very promising anticancer activity. The target compounds contain methoxystyryl fragment introduced in different position of benzoxazolone or benzothiazolone ring. Varying the reaction conditions and reagents, the stilbene derivatives were obtained by the olefination methodology. The cytotoxicity of the synthetic analogues was evaluated on a panel of human cancer cell lines. Based on the results obtained in pharmacological screening 6-styrylbenzoxa(thia)zolones were selected as lead compounds for further in vitro and in vivo investigations. As close structural analogues of the lead stilbenes the corresponding benzophenone derivatives were synthesized. The replacement of the double bond between the two aromatic rings with a carbonyl group reveals an opportunity for new potential anticancer agents. It is important to note that the carbonyl group keeps the two rings in a quasi "cis" orientation, which is important for the biological activity. Two synthetic routes were developed by us for the preparatio of vascular disrupting agent combretastatin A-4. A new approach for the synthesis of stilbene is the method based on the Colvin rearrangement of phenstatin /benzophenone analogue of CA-4/ to the corresponding diarylalkyne followed by stereoselective reduction to CA-4. The applicability of this method was confirmed by the preparation of the lead heterocyclic stilbenes. |
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| Физически характеристики: |
44 с. с ил. 21 см |
| Библиография: |
Библиогр. с. 42-43 |