Evaluation of Novel Spiro-1,4-dihydropyridine Derivatives as Potent Antimicrobial and Anticancer Agents

Objective: Spirooxindole derivatives are emerging as key building blocks in drug discovery due to their diverse biological activities, including antineoplastic, antibiotic, cytostatic, monoamine transporter inhibition, bradykinin antagonism, and cell cycle inhibition. Methods: Given the broad spectrum of biological activities associated with spiroindoles, pyrimidopyrimidines, and thiazolopyrimidines, we aimed to design and synthesize a novel system integrating these bioactive rings within a single molecular framework to assess their potential additive biological effects. Results and Discussion: Among the synthesized novel spiro-1,4-dihydropyridine (DHP) derivatives (IVa–IVf), compounds (IVc), (IVe), and (IVf) exhibited excellent activity against Staphylococcus aureus and Klebsiella pneumoniae. Additionally, compounds (IVb), (IVc), (IVe), and (IVf) demonstrated significant antifungal activity against Aspergillus niger. Of all tested compounds, spiro-1,4-DHP derivative (IVf) showed the highest cytotoxic activity against the HepG2 cell line, with an IC50 value of 13.6 and 2.39 µg/mL, respectively, indicating strong anticancer potential. Conclusions: These findings suggest that the designed compounds exhibit excellent antibacterial, antifungal, and anticancer activities, making them promising candidates for the development of novel pharmaceutical agents for the treatment of bacterial and fungal infections as well as cancer.