Abstract
Novel spiro acenaphthylene pyrrolo[1,2-b]isoquinoline/pyrrolidine hybrids have been achieved through Pictet-Spengler/Eschweiler-Clarke reactions depending on the substitution in the benzyl ring. The in vitro biological efficacy of N-methyl spiropyrrolidine derivatives toward different cancer and non-cancer cell lines revealed that these novel spiro heterocyclic hybrids induced cancer cell death at moderate concentrations, while slight reduction in non-cancer cell viability at the higher concentrations. The analysis of cancer cells proved that the major pathway of cell death is apoptosis and in addition, the role of caspases is confirmed by the appearance of fluorescent cells in microscopic images. Therefore, this study indicates a sustainable way of treating cancer cells by inducing apoptotic pathways and associated caspases, while simultaneously protecting the non-cancer cells.
Highlights
Cancer is a genetic disorder and its occurrence to the healthy normal tissues causes an abnormal growth called the tumors and further the affected cells lose their regular functioning, ability to grow, and division
The extent of genetic disorder can be different even for similar types of cells they live within the same tissue and in addition, the response of normal cell can be different toward the genetic changes than the corresponding cancer cells
The healthy normal cells are mostly immune toward some therapeutic drugs and this resistant rate to the normal cells is quite high as compared against the cancer diseased cells (Cattley and Radinsky, 2004; Horsman and Vaupel, 2016)
Summary
Cancer is a genetic disorder and its occurrence to the healthy normal tissues causes an abnormal growth called the tumors and further the affected cells lose their regular functioning, ability to grow, and division. It is pertinent to note that hybrid anticancer agents displayed better specificity, a superior aptitude to overcome drug-resistance mechanisms, better patient compliance and reduced side effects (Yang and Fu, 2015) Prompted by these reports, we explore in the present investigation the synthesis of some novel spiro heterocyclic hybrids via Pictet-Spengler or Eschweiler-Clarke reactions depending on the substitution in the benzyl ring of the azomethine ylide. The azomethine ylide with no substitution on the aryl ring proceeded via Pictet-Spengler route to furnish the spiro acenaphthylene pyrrolo[1,2-b]isoquinoline hybrids as anticipated, while the azomethine ylide substituted with 4OH group progressed via Eschweiler-Clarke route affording the unpredicted N-methylated spiro acenaphthylene-pyrrolidine heterocyclic hybrids These derivatives were tested toward their biological efficiency by means of in vitro cell culture assays. For the in vitro studies, the derivatives were first tested for the cell viability and proliferation in the presence of different cancer and non-cancer cells and further the active role played by the apoptosis pathway to bring the cancer cell to death was studied
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