Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity
A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins <b>1a</b>–<b>b</b>, a number of α-amino acids <b>2a</b>–<b>e</b> and (E)-2-aryl-1-nitroethenes <b>3a</b>–<b>e</b> in a...
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/18/6503 |
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| author | Richa Sharma Lalit Yadav Ali Adnan Nasim Ravi Kant Yadav Rui Hong Chen Neha Kumari Fan Ruiqi Ashoke Sharon Nawal Kishore Sahu Sirish Kumar Ippagunta Paolo Coghi Vincent Kam Wai Wong Sandeep Chaudhary |
| author_facet | Richa Sharma Lalit Yadav Ali Adnan Nasim Ravi Kant Yadav Rui Hong Chen Neha Kumari Fan Ruiqi Ashoke Sharon Nawal Kishore Sahu Sirish Kumar Ippagunta Paolo Coghi Vincent Kam Wai Wong Sandeep Chaudhary |
| author_sort | Richa Sharma |
| collection | DOAJ |
| description | A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins <b>1a</b>–<b>b</b>, a number of α-amino acids <b>2a</b>–<b>e</b> and (E)-2-aryl-1-nitroethenes <b>3a</b>–<b>e</b> in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using <sup>1</sup>H and <sup>13</sup>C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound <b>4l</b> was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3′-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3′-oxindoles] analogs <b>4a</b>–<b>w</b> against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3′-oxindoles], while five compounds (<b>4c</b>, <b>4f</b>, <b>4m</b>, <b>4q</b>, <b>4t</b>) (IC<sub>50</sub> = 34.99–47.92 µM; SI = 0.96–2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (<b>4c</b>, <b>4f</b>, <b>4k</b>, <b>4m</b>, <b>4q</b>, <b>4t</b>) (IC<sub>50</sub> = 41.56–86.53 µM; SI = 0.49–0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC<sub>50</sub> = 100 µM) and chloroquine (IC<sub>50</sub> = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC<sub>50</sub> = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC<sub>50</sub> = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line]. |
| first_indexed | 2024-03-10T22:25:40Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T22:25:40Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f46affc7e4bb4469976a8ad1e484bcb32023-11-19T12:08:18ZengMDPI AGMolecules1420-30492023-09-012818650310.3390/molecules28186503Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer ActivityRicha Sharma0Lalit Yadav1Ali Adnan Nasim2Ravi Kant Yadav3Rui Hong Chen4Neha Kumari5Fan Ruiqi6Ashoke Sharon7Nawal Kishore Sahu8Sirish Kumar Ippagunta9Paolo Coghi10Vincent Kam Wai Wong11Sandeep Chaudhary12Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, IndiaLaboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, IndiaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, ChinaLaboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, IndiaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, ChinaDepartment of Applied Chemistry, Birla Institute of Technology Mesra, Ranchi 835215, Jharkhand, IndiaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, ChinaDepartment of Applied Chemistry, Birla Institute of Technology Mesra, Ranchi 835215, Jharkhand, IndiaLaboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, IndiaDepartment of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, IndiaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, ChinaDr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, ChinaLaboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, IndiaA novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins <b>1a</b>–<b>b</b>, a number of α-amino acids <b>2a</b>–<b>e</b> and (E)-2-aryl-1-nitroethenes <b>3a</b>–<b>e</b> in a chemo/regio-selective manner using [3+2] cycloaddition (Huisgen) reaction under microwave irradiation conditions. The structure elucidation of all the synthesized spirooxindoles were done using <sup>1</sup>H and <sup>13</sup>C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound <b>4l</b> was used to assign the stereochemical arrangements of the groups around the pyrrolidine ring in spiro[pyrrolidine-2,3′-oxindoles] skeleton. The in vitro anticancer activity of spiro[pyrrolidine-2,3′-oxindoles] analogs <b>4a</b>–<b>w</b> against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines shows promising results. Out of the 23 synthesized spiro[pyrrolidine-2,3′-oxindoles], while five compounds (<b>4c</b>, <b>4f</b>, <b>4m</b>, <b>4q</b>, <b>4t</b>) (IC<sub>50</sub> = 34.99–47.92 µM; SI = 0.96–2.43) displayed significant in vitro anticancer activity against human lung (A549) cancer cell lines, six compounds (<b>4c</b>, <b>4f</b>, <b>4k</b>, <b>4m</b>, <b>4q</b>, <b>4t</b>) (IC<sub>50</sub> = 41.56–86.53 µM; SI = 0.49–0.99) displayed promising in vitro anticancer activity against human liver (HepG2) cancer cell lines. In the case of lung (A549) cancer cell lines, these compounds were recognized to be more efficient and selective than standard reference artemisinin (IC<sub>50</sub> = 100 µM) and chloroquine (IC<sub>50</sub> = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC<sub>50</sub> = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC<sub>50</sub> = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].https://www.mdpi.com/1420-3049/28/18/6503anticancerspirooxindole[3+2] cycloadditionazomethine ylidemicrowave |
| spellingShingle | Richa Sharma Lalit Yadav Ali Adnan Nasim Ravi Kant Yadav Rui Hong Chen Neha Kumari Fan Ruiqi Ashoke Sharon Nawal Kishore Sahu Sirish Kumar Ippagunta Paolo Coghi Vincent Kam Wai Wong Sandeep Chaudhary Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity Molecules anticancer spirooxindole [3+2] cycloaddition azomethine ylide microwave |
| title | Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity |
| title_full | Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity |
| title_fullStr | Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity |
| title_full_unstemmed | Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity |
| title_short | Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity |
| title_sort | chemo regio selective synthesis of novel functionalized spiro pyrrolidine 2 3 oxindoles under microwave irradiation and their anticancer activity |
| topic | anticancer spirooxindole [3+2] cycloaddition azomethine ylide microwave |
| url | https://www.mdpi.com/1420-3049/28/18/6503 |
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