Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity

Herein we present the regio- and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins via intermolecular [3 + 2] cycloaddition reaction. The presented approach is complementary to existing ones and provides an easy entry to the otherwise inaccessible derivatives. Add...

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Main Authors: Valeriia V. Sennikova, Alena V. Zalaltdinova, Yulia M. Sadykova, Ayrat R. Khamatgalimov, Almir S. Gazizov, Alexandra D. Voloshina, Anna P. Lyubina, Syumbelya K. Amerhanova, Julia K. Voronina, Elena A. Chugunova, Nurbol O. Appazov, Alexander R. Burilov, Michail A. Pudovik
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/22/14348
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author Valeriia V. Sennikova
Alena V. Zalaltdinova
Yulia M. Sadykova
Ayrat R. Khamatgalimov
Almir S. Gazizov
Alexandra D. Voloshina
Anna P. Lyubina
Syumbelya K. Amerhanova
Julia K. Voronina
Elena A. Chugunova
Nurbol O. Appazov
Alexander R. Burilov
Michail A. Pudovik
author_facet Valeriia V. Sennikova
Alena V. Zalaltdinova
Yulia M. Sadykova
Ayrat R. Khamatgalimov
Almir S. Gazizov
Alexandra D. Voloshina
Anna P. Lyubina
Syumbelya K. Amerhanova
Julia K. Voronina
Elena A. Chugunova
Nurbol O. Appazov
Alexander R. Burilov
Michail A. Pudovik
author_sort Valeriia V. Sennikova
collection DOAJ
description Herein we present the regio- and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins via intermolecular [3 + 2] cycloaddition reaction. The presented approach is complementary to existing ones and provides an easy entry to the otherwise inaccessible derivatives. Additionally, the unprecedented pathway of the reaction of 4-hydroxycoumarin with azomethine ylides is described. The anti-cancer activity of the obtained compounds was tested in vitro, the most potent compound being 2.6-fold more active against the HuTu 80 cell line than the reference 5-fluorouracil, with a selectivity index > 32.
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spelling doaj.art-e2f5dec6be0f4855b4eef359fc8e23c52023-11-24T08:42:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221434810.3390/ijms232214348Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer ActivityValeriia V. Sennikova0Alena V. Zalaltdinova1Yulia M. Sadykova2Ayrat R. Khamatgalimov3Almir S. Gazizov4Alexandra D. Voloshina5Anna P. Lyubina6Syumbelya K. Amerhanova7Julia K. Voronina8Elena A. Chugunova9Nurbol O. Appazov10Alexander R. Burilov11Michail A. Pudovik12Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaN.S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninsky Ave. 31, 119991 Moscow, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaKorkyt Ata Kyzylorda State University, 29A Aiteke Bi St., Kyzylorda 120014, KazakhstanArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzova str. 8, 420088 Kazan, RussiaHerein we present the regio- and diastereoselective synthesis of novel pyrrolidine-fused spiro-dihydrophosphacoumarins via intermolecular [3 + 2] cycloaddition reaction. The presented approach is complementary to existing ones and provides an easy entry to the otherwise inaccessible derivatives. Additionally, the unprecedented pathway of the reaction of 4-hydroxycoumarin with azomethine ylides is described. The anti-cancer activity of the obtained compounds was tested in vitro, the most potent compound being 2.6-fold more active against the HuTu 80 cell line than the reference 5-fluorouracil, with a selectivity index > 32.https://www.mdpi.com/1422-0067/23/22/14348phosphacoumarinazomethine ylidecycloadditionanti-cancercytotoxicityquantum chemistry
spellingShingle Valeriia V. Sennikova
Alena V. Zalaltdinova
Yulia M. Sadykova
Ayrat R. Khamatgalimov
Almir S. Gazizov
Alexandra D. Voloshina
Anna P. Lyubina
Syumbelya K. Amerhanova
Julia K. Voronina
Elena A. Chugunova
Nurbol O. Appazov
Alexander R. Burilov
Michail A. Pudovik
Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
International Journal of Molecular Sciences
phosphacoumarin
azomethine ylide
cycloaddition
anti-cancer
cytotoxicity
quantum chemistry
title Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
title_full Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
title_fullStr Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
title_full_unstemmed Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
title_short Diastereoselective Synthesis of Novel Spiro-Phosphacoumarins and Evaluation of Their Anti-Cancer Activity
title_sort diastereoselective synthesis of novel spiro phosphacoumarins and evaluation of their anti cancer activity
topic phosphacoumarin
azomethine ylide
cycloaddition
anti-cancer
cytotoxicity
quantum chemistry
url https://www.mdpi.com/1422-0067/23/22/14348
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