Functionalized N-Pyridinylmethyl Engrafted Bisarylmethylidenepyridinones as Anticancer Agents

Abstract

Structurally interesting N-pyridinylmethyl engrafted bisarylmethylidenepyridinones with high functionality have been constructed in good yield. The structural interpretation of these compounds has been done with the aid of spectroscopic analysis and further established by single crystal X-ray diffraction studies. Following physical characterization, the synthesized compounds were tested for their in vitro anticancer activity against HepG2 cancer cells and it was found that all of the compounds exhibited some level of activity. We observed a significant level of cell viability losses to the cancer cells, while only smaller losses to the non-cancer cells were observed. Besides, the mechanistic investigation of toxicology revealed that the cancer cells were undergoing apoptotic pathway, induced by the generation of oxidative stress and the involvement of caspases. The analysis provides preliminary evidence for the successful control of cancer cells with a minimal effect on healthy normal cells because of the high IC50 levels and cell death mechanisms.

In Vitro Molecular Biology Studies of Spirooxindole Heterocyclic Hybrids

“…The selection of cell lines and all the assay protocols for testing the anticancer activity and intracellular mechanisms of spirooxindole-pyrrolidine heterocyclic hybrids were in accordance with our recently published article [30]. The derivatives 1(a-h) with a range of concentrations (12.5-200 µg/mL) were first tested against HepG2 cancer cells over an incubation period of 24-48 h. From those studies, the two most active compounds (1b and 1f) were carried over to test for cell viability and proliferation against the L929 noncancer cell line.…”

“…We presume the molecular hybridization of spirooxindole, pyrrolidine, piperidone, and N-pyridy units embedded with an α,β-unsaturated ketone moiety into new single hybrid architectures, with preselected activities of the original individual subunits that would enhance the biological profiles of new constructs. In one of our recent studies, we investigated the biological potential of N-pyridyl 4-piperidones embedded with an α,β-unsaturated ketone moiety [30]. As a continuation, we present our findings of N-pyridyl-substituted spirooxindole-pyrrolidine heterocyclic hybrids constructed through the aforementioned N-pyridyl 4-piperidone α,β-unsaturated ketones and their molecular biology activities towards cancer and noncancer cells.…”

A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids

“…In our initial attempt, the synthesis of N-unsubstituted bisarylmethylidene-tetrahydropyridinones 3 (a-h) was performed according to the literature report as provided by Dimmock et al [26]. With the compounds 3 (a-h) in hand, the dipolarophiles and N-substituted bisarylmethylidene-tetrahydropyridinones 5 (a-h) required for the present study were synthesized in a 85-90% yield range through the alkylation of 3 (a-h) with 2-(chloromethyl)pyridine hydrochloride in the presence of K 2 CO 3 (Scheme 1) [27,28]. The azomethine ylide was generated in situ from isatin and phenylglycine via decarboxylative condensation.…”