Pyrrolidine Derivatives in Modern Drug Discovery: Emerging Structure Activity Relationships and Dual Antidiabetic–Anticancer Potential

Abstract

Pyrrolidine, a five-membered nitrogen-containing heterocycle, has emerged as an important structural motif in medicinal chemistry owing to its pronounced pharmacological versatility, conformational flexibility, and favorable physicochemical properties. In recent years, pyrrolidine-based compounds have attracted considerable attention for their therapeutic potential in the management of diabetes and cancer, two major global health challenges. This review compiles and critically analyzes recent advances in the design, synthesis, and biological evaluation of pyrrolidine derivatives exhibiting antidiabetic and anticancer activities. Particular emphasis is placed on structure-activity relationship (SAR) studies, highlighting how subtle modifications in substitution patterns, electronic properties, and steric factors markedly influence biological performance. Numerous studies demonstrate that strategic functionalization at key positions of the pyrrolidine ring leads to enhanced selectivity, improved inhibition of carbohydrate-metabolizing enzymes (including α-glucosidase, α-amylase, and DPP-IV), and pronounced antiproliferative effects against a range of cancer cell lines. By integrating important findings reported over the past decade (2013-2025), this review underscores the potential of pyrrolidine derivatives as dual-action therapeutic agents and provides a coherent framework to guide the rational design of future drug candidates.