The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential

•The article describes the general aspects of antitumor bis(hydroxymethyl)pyrroles.•General synthetic route for constructing targeted derivatives are described.•Several bis(hydroxymethyl)pyrrole derivatives show potent antitumor activities.•SARs of the synthesized analogs are discussed.•Further modifications of A ring may generate lead compound for clinical applications.

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure–activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed.

Graphical abstractThis review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs having potential antitumor activity.Figure optionsDownload full-size imageDownload as PowerPoint slide