Quinazoline Based HDAC Dual Inhibitors as Potential Anti-Cancer Agents

Abstract

Cancer is the most devastating disease and second leading cause of death around the world. Despite scientific advancements in the diagnosis and treatment of cancer which can include targeted therapy, chemotherapy, endocrine therapy, immunotherapy, radiotherapy and surgery in some cases, cancer cells appear to outsmart and evade almost any method of treatment by developing drug resistance. Quinazolines are the most versatile, ubiquitous and privileged nitrogen bearing heterocyclic compounds with a wide array of biological and pharmacological applications. Most of the anti-cancer agents featuring quinazoline pharmacophore have shown promising therapeutic activity. Therefore, extensive research is underway to explore the potential of these privileged scaffolds. In this context, a molecular hybridization approach to develop hybrid drugs has become a popular tool in the field of drug discovery, especially after witnessing the successful results during the past decade. Histone deacetylases (HDACs) have emerged as an important anti-cancer target in the recent years given its role in cellular growth, gene regulation, and metabolism. Dual inhibitors, especially based on HDAC in particular, have become the center stage of current cancer drug development. Given the growing significance of dual HDAC inhibitors, in this review, we intend to compile the development of quinazoline based HDAC dual inhibitors as anti-cancer agents.

An insight into therapeutic efficacy of heterocycles as histone‐modifying enzyme inhibitors that targets cancer epigenetic pathways

“…These are mood stabilizers and anti‐epileptics, used for psychiatry and neurology problems (Tasneem et al, 2021; Dekker & Haisma, 2009., Bass et al, 2021). For the past couple of years, these have shown significant inhibitory potential for cancer, inflammatory diseases, and other disorders (Dhuguru & Ghoneim, 2022; Cheng et al, 2019; Slaughter et al, 2021). Epigenetic drugs such as HDAC inhibitors selectively target class I and IV HDAC enzymes which results in the inhibition of cell proliferation, terminal differentiation, and apoptosis (Citron & Fabris, 2020; Qiu et al, 2021; Ren & Gao, 2021).…”

Transition metal(ii) complexes of halogenated derivatives of (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline: structure, antioxidant activity, DNA-binding DNA photocleavage, interaction with albumin andin silicostudies

“…The M : L ratio was 1 : 2 for complexes 1, 2 and 5 and 1 : 1 for complexes 3, 4 and 6. The coordination compounds were characterized by IR, 1 H NMR and UV-vis spectroscopy. All crystal structures were characterized by single-crystal X-ray crystallography.…”

“…4-Hydrazonyl quinazolines are compounds that hybridize two pharmacophore cores: a quinazoline 1,2 and a hydrazone. 3,4 Quinazolines constitute a class of heterocycles that contain two fused aromatic benzene and pyrimidine rings and exhibit a plethora of biological activities.…”

Anticancer Biological Profile of Some Heterocylic Moieties-Thiadiazole, Benzimidazole, Quinazoline, and Pyrimidine

“…Quinazoline nitrogen-bearing aromatic heterocycle compound made up of fused two six-membered rings-benzene and pyrimidine which is prepared by Gabriel in 1903. The quinazoline ring can occur in four isomeric forms depending on the position of the nitrogen atoms: quinazoline, quinoxaline, cinnolines, and pthalazines [13]. Quinazoline synthesis methods are divided into five categories based on whether they are traditional or innovative, including Aza-reaction, Microwave-assisted reaction, Metal-catalyzed reaction, Ultrasoundpromoted reaction, and Phase-transfer catalysis [14].…”