Sustainable Synthesis and Biological Aspects of Pyrrolobenzodiazepine Derivatives: An Insight Into Current Developments, Structure-Activity Relationships, and Clinical Studies

Abstract

Pyrrolobenzodiazepine is tricyclic ring system containing five-, six-, and seven-membered nitrogen heterocycles in the molecular framework. This is a privileged pharmacophore found in pharmaceutical drugs and natural products. However, researchers worldwide are exploring green synthetic methods to develop novel bioactive agents to curb undesirable health effects in humans and aquatic animals. In view of this, various sets of pyrrolobenzodiazepines were synthesized by modulating the ring position or by adding other pharmacophores to enhance the molecules’ efficacy. This review is primarily concerned with retrosynthetic, functionalization, and green synthesis of pyrrolobenzodiazepines (1965–2025), followed by an in-depth discussion of their various biological properties, highlighting structure–activity relationships, molecular docking, and in vitro and in vivo studies on pyrrolobenzodiazepines. This review provides an overview of the synthesis, structural characteristics, and diverse spectrum of biological properties, which will surely open a new window for the design and development of potent pyrrolobenzodiazepine-based drugs in future research.