Anticancer Potential of 1,3‐Benzodioxole Derivatives—A Systematic Review

ABSTRACT

The privileged pharmacophoric moiety 1,3‐benzodioxole (BDO) was first identified in 1844 from a natural origin and first synthesized in 1869 for commercial purposes. The chemical and biological diversity of BDO analogues has greatly benefited drug design for various pathologies, including cancer. In this review, we discuss the oncolytic profiles of distinguished BDO derivatives, classified as natural and synthetic analogues, and further categorized chemically into 5‐, 4‐, 4,5‐, and 5,6‐substituted and fused derivatives. Moreover, we enumerate the structure–activity relationships, molecular targets, binding potency, and cytotoxic profiles of various BDO derivatives reported during the last 25 years. At the end, we summarize that the 5‐substituted BDO derivatives have been explored extensively and exhibit appreciable cytotoxic potency, whereas the heterocyclic ring‐fused BDO analogues have exhibited excellent in vivo antitumor profiles. Furthermore, the anticancer activity profiles of the best‐in‐class BDO derivatives are summarized along with the limitations and research gaps. In the future, drug design strategies that incorporate bulky substituents at position 2 and electron‐donating/withdrawing groups at positions 5 and/or 4 of BDO could yield novel and potent BDO‐based anticancer agents.