Recent Advances in β-lactam Derivatives as Potential Anticancer Agents

Abstract

Cancer, accounts for around 10 million deaths annually, is the second leading cause of death globally. The continuous emergency of drug-resistant cancers and the low specificity of anticancer agents are the main challenges in the control and eradication of cancers, so it is imperative to develop novel anticancer agents. Immense efforts have been made in developing new lead compounds and novel chemotherapeutic strategies for the treatment of various forms of cancers in recent years. β-Lactam derivatives constitute versatile and attractive scaffolds for the drug discovery since these kinds of compounds possess a variety of pharmacological properties, and some of them exhibited promising potency against both drug-sensitive and drug-resistant cancer cell lines. Thus, β-lactam moiety is a useful template for the development of novel anticancer agents. This review will provide an overview of β-lactam derivatives with the potential therapeutic application for the treatment of cancers covering articles published between 2000 and 2020. The mechanisms of action, the critical aspects of design and structureactivity relationships are also discussed.

Sequence-based drug design as a concept in computational drug design

“…In addition, the widespread use of β-lactams can increase the risk of antibiotic resistance, mainly due to the production of β-lactamase 50 . Although compounds with β-lactam rings have been reported to exhibit anticancer activity 51 and have been used in drug development, such as cholesterol absorption inhibitors and vasopressin V1a antagonists 52 , vigilance is necessary when developing non-antibacterial agents to avoid these risks.…”

Cefepime, a Cephalosporin, Induces the Apoptosis and Oxidative Stress in Nb2a Neuroblastoma Cells

“…They have strong antibacterial effects with minimal toxicity on human cells except for allergic reactions (He at al, 2021). Several evidence shows the potential of ß-lactam antibiotics as anticancer agents specifically targeting tumor cells (Kuhn et al, 2004;Zhang and Jia, 2020). Here we examined the anticancer effect of cefepime, a fourth generation cephalosporin, on the neuroblastoma cells in vitro.…”

Synthesis of α‐Quaternary β‐Lactams via Copper‐Catalyzed Enantioconvergent Radical C(sp3)−C(sp2) Cross‐Coupling with Organoboronate Esters

“…[18] We next investigated the scope of alkyl bromides for the reaction (Table 2). A range of substituents, such as the functionalized benzyl ring (1)(2)(3)(4)(5), homobenzyl ring ( 6), purely aliphatic chain (7), and cyclic ring (8)(9)(10)(11) on the nitrogen of α-bromo-β-lactams was tolerated to afford the coupling products in good yields with 93-99 % ee. Phenyl rings possessing electron-donating or -withdrawing substituents at the meta and para positions of α-bromo-β-lactams were well compatible with the reaction conditions to deliver 12-17 in up to 85 % yield with excellent ee.…”

“…We hope that the developed catalytic cycle would open up new vistas for more enantioconvergent cross-coupling reactions.Chiral β-lactams are core structures in an array of widely used antibiotics (penicillin, cephalosporins) and many synthetic methods have been developed for their assembly. [1] Due to the antibiotic resistance, the need for new β-lactam skeletons is growing and it has further led to the discovery of β-lactams possessing new potent activities, such as anticancer, [2] antifungal, [3] cholesterol-controlling, [4] etc. Among them, chiral β-lactams bearing an α-quaternary stereocenter are not only an important subunit of this family but also valuable synthons for building blocks in organic synthesis (Scheme 1A).…”