Natural products and synthetic analogues in the prevention and management of urolithiasis: A comprehensive review

Abstract :

Urolithiasis is a multifactorial renal disorder characterized by calcium oxalate crystallization, oxidative stress, inflammation, urinary supersaturation, and enzyme-mediated pathological processes. Recent developments in synthetic analogues and natural lead compounds investigated for kidney stone therapy and prevention are critically summarized in this study. Along with nephroprotective, antioxidant, anti-inflammatory, and diuretic properties, 25 natural compounds showed anti-urolithiatic efficacy mainly by suppression of calcium oxalate nucleation, aggregation, and growth. By promoting the development of less adherent calcium oxalate dihydrate and reestablishing urinary citrate and magnesium levels, several extracts also altered crystal shape. In addition, twenty-five synthesized drugs were classified according to dominating processes, such as enzyme-targeted tactics, diuretic-mediated urine regulation, antioxidant-supported crystal suppression, and direct crystallization inhibition. Strong calcium oxalate inhibitory potential was demonstrated by synthetic scaffolds such as phthalimides, barbiturates, imidazoles, benzene sulphonamides, and Schiff bases, while hybrids targeting urease and carbonic anhydrase showed low-micromolar to nanomolar enzyme inhibition, addressing urinary pH imbalance and infection-associated lithogenesis. Relationships between structure and action demonstrated how crucial heterocyclic frameworks, sulfonamide moieties, and electron-donating substituents are for increasing efficacy. The importance of multi-target techniques is shown by the fact that natural and synthetic candidates work together through complementary pathways, including crystal modification, oxidative stress attenuation, urine parameter normalization, and enzyme inhibition. To turn these candidates into successful antiurolithiatic treatments, more pharmacokinetic profiling, safety assessment, and clinical validation are necessary, even if many leads have encouraging preclinical efficacy.

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Citation :

Bhavana KS, et al. Natural products and synthetic analogues in the prevention and management of urolithiasis: A comprehensive review. Mediterr J Pharm Pharm Sci. 2026; 6(2): 74-93. [Article number: 255]. https://doi.org/10.5281/zenodo.20793831