Design, Synthesis, and In Vitro Antiproliferative Activity of Hydantoin and Purine Derivatives with the 4-Acetylphenylpiperazinylalkyl Moiety.

Agnieszka Zagórska,Magdalena Mielczarek-Puta,Marek Bajda,Anna Czopek,Marta Struga,Anna Jaromin,Dorota Stary

doi:10.3390/ma14154156

Abstract

Cancer represents one of the most serious health problems and the second leading cause of death around the world. Heterocycles, due to their prevalence in nature as well as their structural and chemical diversity, play an immensely important role in anti-cancer drug discovery. In this paper, a series of hydantoin and purine derivatives containing a 4-acetylphenylpiperazinylalkyl moiety were designed, synthesized, and biologically evaluated for their anticancer activity on selected cancer cell lines (PC3, SW480, SW620). Compound 4, a derivative of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione, was the most effective against SW480, SW620, and PC3 cancer cell lines. Moreover, 4 has high tumor-targeting selectivity. Based on docking studies, it was concluded that R isomers of 3′,4′-dihydro-2′H-spiro[imidazolidine-4,1′-naphthalene]-2,5-dione could be further studied as promising scaffolds for the development of thymidine phosphorylase inhibitors.

Highlights

Accepted: 23 July 2021Cancer is a disease in which the control of growth is lost in one or more cells, leading to hematological malignancies or a solid mass of cells known as tumors [1]
The culture medium of HMEC-1 cells was supplemented with glutamine (1 mM) and microvascular growth supplement (5%) (MVGS; Gibco, USA)
We tested the antiproliferative effect of two groups of compounds against different human cancer cell lines, namely prostate (PC3) and colon (SW480, SW620)

Summary

Introduction

Cancer is a disease in which the control of growth is lost in one or more cells, leading to hematological malignancies or a solid mass of cells known as tumors [1]. Organization (WHO) provides recent information on frequency, mortality, and survival expectancy of the 15 leading types of cancers worldwide. The epidemiological information and the gradual pattern of malignant growth recurrence, commonness, and mortality expected over the 40 years highlight that cancer will stay a scourge for a long time to come [2]. The WHO estimated that, in the four decades, cancer deaths are expected to overtake those for ischemic heart disease, the current leading cause of global deaths, with a 2.08-fold increase by the year 2060 [3]. The hallmarks of cancer include self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replication potential, sustained angiogenesis, tissue invasion and metastasis, and inactivation of systems that regulate cellular response to DNA damage.

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