All that glitters is not gold: Panning cytotoxic natural products and derivatives with a fused tricyclic backbone by the estimation of their leadlikeness for cancer treatment

• Published in: European journal of medicinal chemistry Vol. 166; pp. 1 - 10
• Main Authors: Klein-Júnior, Luiz Carlos, Corrêa, Rogério, Vander Heyden, Yvan, Cechinel Filho, Valdir
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 15.03.2019
• Subjects: Cancer; Cytotoxic; Hit-to-lead; Leadlikeness; Xanthone; Xanthone; Cytotoxic; Hit-to-lead; Leadlikeness; Cancer
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.01.028

Tricyclic compounds call the attention because of their pharmacological properties, and are considered a preferred platform for the development of drugs. Especially, in cancer treatment, these planar compounds are known for their ability to stack with DNA base pairs, acting as intercalators. In this sense, natural products (NPs) are a prodigal source of polycyclic compounds, comprising classes, such as carbolines, anthraquinones and xanthones. However, most of these compounds lack suitable physico-chemical properties, compatible to oral bioaviability. In this perspective, this paper aims to overview the role of tricyclic cores in the development of cytotoxic compounds, focusing on the leadlikeness estimation of the most prominent NP classes and their synthetic derivatives. [Display omitted] •Tricyclic natural products and derivatives are important cytotoxic compounds.•Most tryciclic compounds (83%) comply the rule of five.•Abietanes, anthraquinones and xanthones cluster with the drugs chemical space.•Xanthones mostly complied for the rule of 5 parameters.•Xanthone backbone is an inspiration for the development of oral anticancer drugs.