Hybrid Molecules with Potential Activity against Drug-resistant Cancer - PART-I.

Abstract

Cancer, which can invade almost all parts of the body, accounts for 18% of all deaths throughout the world and ranks as one of the leading causes of death among non-communicable diseases [1, 2]. Since cancers have a high chance of curing if appropriate treatment is provided, anticancer agents are critical for tumor therapy. However, the continuous emergency of drug-resistant cancer has already become one of the major challenges in the control and eradication of cancers [3, 4]. Therefore, dis-covering the next wave of anticancer agents with high potency against drug-resistant forms is vital. Coumarin, podophyllotoxin, hydroxamic acid, ferrocene, and acridine derivatives cannot only in-hibit tumor proliferation, invasion, and metastasis by acting on multiple intracellular signaling net-work molecules but also have reverse cancer multidrug resistance effect [5-9]. Moreover, many cur-rent available anticancer agents own these pharmacophores, demonstrating the potential of these pharmacophores to fight against various cancers, including drug-resistant forms. Hybridization repre-sents a promising strategy to develop novel anticancer agents since hybrid molecules can simultaneously act on dual or multi-ple cancer-relevant targets, such as metalloproteinases, ATP binding cassette subfamily G member 2 (ABCG2), human mito-chondrial peptide deformylase, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), P-glycoprotein (P-gp), tubulin, and vascular endothelial growth factor (VEGF) [10, 11]. Thus, hybrid molecules can increase specificity, reduce side effects, improve patient compliance, and overcome drug resistance [12]. Accordingly, a combination of coumarin, podophyl-lotoxin, hydroxamic acid, ferrocene, or acridine with other anticancer pharmacophores is an attractive strategy for the discov-ery of novel anticancer agents with potent activity against various cancers, especially drug-resistant forms. This special issue focuses on the current scenario of coumarin, podophyllotoxin, hydroxamic acid, ferrocene, and acridine hybrids with in vitro and in vivo anticancer potential. The mechanisms of action, the critical aspects of design, and structure-activity relationships are also discussed to pave the way for the further rational design of novel candidates with excellent effi-ciency against drug-resistant cancers.