Abstract

SYNTHESIS AND BIOLOGICAL INVESTIGATION OF NOVEL SPIROOXINDOLE DERIVATIVES PREPARED BY 1, 3-DIPOLAR CYCLOADDITION

Krishnamalar G.*

ABSTRACT

Spirooxindole derivatives constitute an important class of heterocyclic compounds owing to their diverse biological activities and broad therapeutic potential. In the present study, a series of novel spirooxindole derivatives were synthesized through a one-pot three-component 1,3-dipolar cycloaddition reaction involving naphthoquinone, isatin derivatives, and azomethine ylides generated in situ from sarcosine or L-proline. The reaction conditions were optimized by varying the reactant ratio, resulting in excellent product yields (82–96%) within a short reaction time. The synthesized compounds were purified by column chromatography and monitored using thin-layer chromatography. Structural characterization was performed using melting point determination, IR spectroscopy, 1H NMR, 13C NMR, mass spectrometry, and HPLC, confirming the successful formation and purity of the desired spirooxindole derivatives. Biological evaluation included invitro anticancer, anti-inflammatory, anti-arthritic, and antimicrobial studies. Anticancer activity was assessed against the HCT116 human colorectal carcinoma cell line using the MTT assay, where selected compounds demonstrated promising cytotoxic activity. Anti-inflammatory activity was investigated by the HRBC membrane stabilization method, while anti-arthritic potential was evaluated using the protein denaturation inhibition assay, with several compounds exhibiting activity comparable to the standard drug diclofenac sodium. Antibacterial and antifungal activities were determined by the disc diffusion method against selected Gram-positive, Gram-negative, and fungal strains, revealing moderate to significant antimicrobial effects. Overall, the synthesized spirooxindole derivatives exhibited encouraging biological properties, demonstrating that the incorporation of suitable substituents into the spirooxindole framework can enhance pharmacological activity. These findings identify the synthesized compounds as promising lead molecules for further optimization and preclinical investigations aimed at developing novel therapeutic agents.

Keywords: Spirooxindoles, 1,3-Dipolar cycloaddition, Azomethine ylide, Anticancer activity, Anti-inflammatory activity, Anti-arthritic activity, Antimicrobial activity, MTT assay, Heterocyclic compounds, Naphthoquinone.