The Syntheses and Medicinal Attributes of Phenanthrenes as Anticancer Agents: A Quinquennial Update

Abstract

: Cancer is a silent killer and remains to pose major health problems globally. Amongst the several biological targets, DNA is one of the most striking targets in cancer chemotherapy. Owing to its planar structure, phenanthrene and its derivatives exhibit potential cytotoxicity by intercalating between the DNA base pairs and by inhibiting the enzymes that are involved in the synthesis of DNA. However, due to the off-target effects and resistance, the development of novel chemotherapeutic agents would be meritorious. In this regard, we detail in the review on the development of phenanthrene-based derivatives reported in the last quinquennial. This review mainly focuses on the synthetic aspects and strategies to procure the fused phenanthrene derivatives such as (i) phenanthroindolizidines, phenanthroquinolizidine, phenanthroimidazoles, podophyllotoxin-based phenanthrenes and dihydrophenanthrodioxine derivatives, (ii) phenanthrene conjugates with other pharmacologically significant pharmacophores and (iii) phenanthrene-metal complexes. This review also edifies their potential in vitro cytotoxicity evaluation against various carcinoma cell lines in submicromolar to nanomolar ranges. Additionally, computational studies and structure-activity relationships (SARs) have also been presented to highlight the essential features of the designed congeners. Thus, this review would aid in the development of novel derivatives in future as potential cytotoxic agents in the field of medicinal chemistry.

Redox- and Charge-State Dependent Trends in 5, 6, and 7-Membered Boron Heterocycles: A Neutral Ligand Coordination Chemistry Approach to Boracyclic Cations, Anions, and Radicals

“…24 Derivatives of phenanthrene have also found use in medicinal chemistry for their anticancer, anti-inflammatory, and antibacterial properties. 25 Researchers have found ways to incorporate various heteroatoms (i.e., N, P, S) into the phenanthrene scaffold, primarily as a means to develop conjugated materials with distinct properties. 26 There are reports of BN-phenanthrenes, 27 boroxophenanthrene, 28 and our laboratory reported a neutral BP-phenanthryne through photolysis of a boraphosphaketene.…”

“…4 The NHC-stabilized boracycle undergoes halide abstraction via the addition of AgSbF 6 to give cationic boracycle 24 (Scheme 3). Reduction via the addition of one or two equivalents of KC 8 lead to the stable radical (25) and anion (26), respectively. Compound 25 is among the most stable Lewis base-stabilized B-PAH radicals, surviving in boiling toluene for at least 1 week.…”

“…We became interested in phenanthrene due to its inherent stability and luminescent properties, which have been valuable for molecular materials and photoredox chemistry . Derivatives of phenanthrene have also found use in medicinal chemistry for their anticancer, anti-inflammatory, and antibacterial properties . Researchers have found ways to incorporate various heteroatoms (i.e., N, P, S) into the phenanthrene scaffold, primarily as a means to develop conjugated materials with distinct properties .…”