Current Topics in Medicinal Chemistry - Volume 21, Issue 19, 2021

Podophyllotoxins, including epipodophyllotoxin derivatives, can act on a diverse array of drug targets in cancer cells and thus possess potent activity against various forms of cancer cell lines, including drug-resistant forms. Moreover, several podophyllotoxin derivatives represented by etoposide and teniposide, have already been approved for cancer therapy, demonstrating podophyllotoxin moiety as a useful pharmacophore for the discovery of novel anticancer agents. This review reports the recent advances in the exploitation of podophyllotoxin derivatives to fight against multidrug-resistant cancer cells. The mechanism of action and structure-activity relationship (SAR) studies are also highlighted.

Cancer is the main cause of death, and the emergence of resistance by cancer cells towards existing anticancer agents is one of the major problems for effective chemotherapy, creating a great demand for the development of novel anticancer drugs. Coumarins, abundantly found in nature, constitute an important class of pharmacological agents possessing physiological activities. The mechanism investigations elucidated that coumarins could lead to self-programmed cancer cell death (apoptosis) via different mechanisms; thereby coumarin-based derivatives possess potential activity against various forms of cancers, including drug-resistant, even multidrug-resistant cancers. This review article describes the recent progress in the discovery, structural modification, structure-activity relationship, and mechanism of action studies of coumarin-based derivatives with potential activity against drug-resistant cancers, covering articles published between 2010 and 2020.

Notwithstanding the noteworthy advances in its treatment, cancer remains one of the most serious threatens to humans across the world. Hydroxamic acid derivatives, the potential inhibitors of Histone Deacetylases (HDACs), could inhibit cancer cell proliferation, induce cell differentiation, apoptosis and autophagy, and suppress angiogenesis, invasion as well as metastasis through diverse signaling pathways. Thus, hydroxamic acid derivatives exhibit promising activity against cancers and are useful scaffolds in modern anticancer drug discovery. The purpose of the present review article is to summarize the recent developments (Jan, 2011-Jan, 2021) in hydroxamic acid derivatives with insights into their in vivo anticancer potential and mechanisms of action.

Cancer, a highly heterogeneous disease at intra/inter patient levels, remains a serious health problem contributing to significant morbidity and mortality worldwide. Despite great progress in clinical treatment, the concern impeding the success of conventional cancer chemotherapy is descending efficacy of anticancer agents due to the development of drug resistance especially multiple drug resistance (MDR). Ferrocene derivatives have a different mode of action to the platinum anticancer drugs, and the ferrocene-phenol hybridferrocifen exhibits potentialactivity againstdrug-resistant cancers. Currently, ferrocifen is in preclinical trial, demonstrating that ferrocene derivatives are useful scaffolds for the development of novel anticancer candidates which are active against drug-resistant cancers. In the present review, the current scenario of ferrocene derivatives including ferrocenemetal complexes, hybrids and other derivatives with antiproliferative potential against drug-resistant cancer cell lines is summarized for further rational design.

Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance, especially multidrug resistance, remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan, 2015 to Feb, 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for a further rational design of novel anticancer agents.