Chemo-/Regio-Selective Synthesis of Novel Functionalized Spiro[pyrrolidine-2,3′-oxindoles] under Microwave Irradiation and Their Anticancer Activity
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
Affiliations
Richa Sharma
Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, India
Lalit Yadav
Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, India
Ali Adnan Nasim
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China
Ravi Kant Yadav
Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, India
Rui Hong Chen
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China
Neha Kumari
Department of Applied Chemistry, Birla Institute of Technology Mesra, Ranchi 835215, Jharkhand, India
Fan Ruiqi
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China
Ashoke Sharon
Department of Applied Chemistry, Birla Institute of Technology Mesra, Ranchi 835215, Jharkhand, India
Nawal Kishore Sahu
Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, India
Sirish Kumar Ippagunta
Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
Paolo Coghi
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China
Vincent Kam Wai Wong
Dr. 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, China
Sandeep Chaudhary
Laboratory of Organic and Medicinal Chemistry (OMC Lab), Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, Rajasthan, India
A novel series of nitrostyrene-based spirooxindoles were synthesized via the reaction of substituted isatins 1a–b, a number of α-amino acids 2a–e and (E)-2-aryl-1-nitroethenes 3a–e 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 1H and 13C NMR and HRMS spectral analysis. The single crystal X-ray crystallographic study of compound 4l 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 4a–w 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 (4c, 4f, 4m, 4q, 4t) (IC50 = 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 (4c, 4f, 4k, 4m, 4q, 4t) (IC50 = 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 (IC50 = 100 µM) and chloroquine (IC50 = 100 µM; SI: 0.03). However, none of them were found to be active as compared to artesunic acid [IC50 = 9.85 µM; SI = 0.76 against lung (A549) cancer cell line and IC50 = 4.09 µM; SI = 2.01 against liver (HepG2) cancer cell line].
