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Prospecting for Novel Plant-Derived Molecules of Rauvolfia serpentina as Inhibitors of Aldose Reductase, a Potent Drug Target for Diabetes and Its Complications

Figure 2

Strategy implemented towards prospecting for novel ARIs from R. serpentina.

R. serpentina extracts are reported to be effective against diabetes and its complications. AR controls the rate-limiting step of polyol pathway, and its inhibition is known to prevent complications of diabetes. Founded in these empirical facts, we propose a hypothesis connecting effectiveness of molecular constituents of plant extracts to a regulatory mechanism central to the disorder. Towards our aim of prospecting for novel ARIs, we compiled a structured library of R. serpentina PDMs, and screened them to obtain ‘best PDMs’ (3). The best PDMs were refined to obtain two ‘PDM leads’ on the basis of their structural stability. Further, 16 more ‘ZINC leads’ were identified by screening structural analogs of these plant-derived leads, and representative analogs were assessed for their structural stability. This prospection study presents a repertoire of plant-derived indole alkaloids, and their analogs, as potential AR inhibitors.

Figure 2