Antineoplastic indole-containing compounds with potential VEGFR inhibitory properties.

Cancer is one of the most significant health challenges worldwide. Various techniques, tools and therapeutics/materials have been developed in the last few decades for the treatment of cancer, together with great interest, funding and efforts from the scientific society. However, all the reported studies and efforts seem insufficient to combat the various types of cancer, especially the advanced ones. The overexpression of tyrosine kinases is associated with cancer proliferation and/or metastasis. VEGF, an important category of tyrosine kinases, and its receptors (VEGFR) are hyper-activated in different cancers. Accordingly, they are known as important factors in the angiogenesis of different tumors and are considered in the development of effective therapeutic approaches for controlling many types of cancer. In this case, targeted therapeutic approaches are preferable to the traditional non-selective approaches to minimize the side effects and drawbacks associated with treatment. Several indole-containing compounds have been identified as effective agents against VEGFR. Herein, we present a summary of the recent indolyl analogs reported within the last decade (2012-2023) with potential antineoplastic and VEGFR inhibitory properties. The most important drugs, natural products, synthesized potent compounds and promising hits/leads are highlighted. Indoles functionalized and conjugated with various heterocycles beside spiroindoles are also considered.

Indole Compounds in Oncology: Therapeutic Potential and Mechanistic Insights.

Cancer remains a formidable global health challenge, with current treatment modalities such as chemotherapy, radiotherapy, surgery, and targeted therapy often hindered by low efficacy and adverse side effects. The indole scaffold, a prominent heterocyclic structure, has emerged as a promising candidate in the fight against cancer. This review consolidates recent advancements in developing natural and synthetic indolyl analogs, highlighting their antiproliferative activities against various cancer types over the past five years. These analogs are categorized based on their efficacy against common cancer types, supported by biochemical assays demonstrating their antiproliferative properties. In this review, emphasis is placed on elucidating the mechanisms of action of these compounds. Given the limitations of conventional cancer therapies, developing targeted therapeutics with enhanced selectivity and reduced side effects remains a critical focus in oncological research.