Current Topics in Medicinal Chemistry - Volume 21, Issue 5, 2021

Drug resistance, including multidrug resistance resulting from different defensive mechanisms in cancer cells, is the leading cause of the failure of the cancer therapy, posing an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potent activity against various cancers, including drug-resistant, even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020 so as to facilitate further rational design of more effective candidates.

The incidence and mortality of cancer continue to grow since the current medical treatments often fail to produce a complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. Heterocycles with potential therapeutic values are of great pharmacological importance, and among them, indazole moiety is a privileged structure in medicinal chemistry. Indazole compounds possess potential anticancer activity, and indazole-based agents such as, axitinib, lonidamine and pazopanib have already been employed for cancer therapy, demonstrating indazole compounds as useful templates for the development of novel anticancer agents. The aim of this review is to present the main aspects of exploring anticancer properties, such as the structural modifications, the structure-activity relationship and mechanisms of action, making an effort to highlight the importance and therapeutic potential of the indazole compounds in the present anticancer agents.

Indole, a heterocyclic organic compound, is one of the most promising heterocycles found in natural and synthetic sources since its derivatives possess fascinating structural diversity and various therapeutic properties. Indole alkaloids, synthetic dimers and hybrids could act on diverse targets in cancer cells, and consequently, possess potential antiproliferative effects on various cancers both in vitro and in vivo. Vinblastine, midostaurin, and anlotinib as the representative of indole alkaloids, synthetic dimers and hybrids respectively, have already been clinically applied to treat many types of cancers, demonstrating indole alkaloids, synthetic dimers and hybrids are useful scaffolds for the development of novel anticancer agents. Covering articles published between 2010 and 2020, this review emphasizes the recent development of indole alkaloids, synthetic dimers and hybrids with potential in vivo therapeutic application for cancers.

Due to the increasing prevalence of cancer year by year, and the complexity and refractory nature of the disease itself, it is required to constantly innovate the development of new cancer treatment schemes. At the same time, the understanding of cancers has deepened, from the use of chemotherapy regimens with high toxicity and side effects, to the popularity of targeted drugs with specific targets, to precise treatments based on tumor characteristics rather than traditional anatomical location classification. In precision medicine, in the view of the specific cancer diseases and their biological characteristics, there is a great potential to develop tissue-agnostic targeted therapy with broad-spectrum anticancer significance. The present review has discussed tissue-agnostic targeted therapy based on the biological and genetic characteristics of cancers, expounded its theoretical basis and strategies for drug development. In addition, the feasible drug targets, FDA-approved drugs, as well as drug candidates in clinical trials have also been summarized. In conclusion, the “tissue-agnostic targeted therapy” is a breakthrough in anticancer therapies.

Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potent activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview of the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.