Regio and stereoselective synthesis of anticancer spirooxindolopyrrolidine embedded piperidone heterocyclic hybrids derived from one-pot cascade protocol

Natarajan Arumugam; Abdulrahman I Almansour; Raju Suresh Kumar; Dhaifallah M Al-Thamili; Govindasami Periyasami; V S Periasamy; Jegan Athinarayanan; Ali A Alshatwi; S M Mahalingam; J Carlos Menéndez

doi:10.1186/s13065-018-0462-x

Regio and stereoselective synthesis of anticancer spirooxindolopyrrolidine embedded piperidone heterocyclic hybrids derived from one-pot cascade protocol

Chem Cent J. 2018 Sep 1;12(1):95. doi: 10.1186/s13065-018-0462-x.

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. anatarajan@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
³ Nanobiotecnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia.
⁴ Department of Atomic and Molecular Physics, MIT Campus, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
⁵ Unidad de Química Orgánica y Farmacéutica, Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense, 28040, Madrid, Spain.

Abstract

Background: Spiropyrrolidine tethered piperidone heterocyclic hybrids were synthesized with complete regio- and stereoselectively in excellent yield via a tandem three-component 1,3-dipolar cycloaddition and subsequent enamine reaction in [bmim]Br. The synthesized compounds were evaluated for their anticancer activity against FaDu hypopharyngeal tumor cells.

Findings: Interestingly, most compounds displayed cytotoxicities similar to the standard anticancer agent bleomycin, with two of them (5a and 5g) being slightly more active than the reference drug.

Conclusion: Synthesized compounds have also been evaluated for their apoptosis-inducing properties in a cancer cell model, finding that treatment with compounds 5a-e led to apoptotic cell death.

Keywords: Antiproliferative activity; Apoptosis induction; Chemo divergent multicomponent reactions; Domino reactions; Piperidone; Spiropyrrolidine.

Grants and funding

Research group No. RG-1438-052./The authors thank the Deanship of Scientific Research at King Saud University for funding this work through research group No. RG-1438-052.