Biological Activity of Quinazolinones

*Awwad A. Radwan and Fars K. Alanazi*

### **Abstract**

The chemical structure of quinazolinones includes benzene ring fused with 2-pyrimidinone (1), 4-pyrimidinone (2) or 2,4-pyrimidinedione (3) ring, and are named as quinazolin-2(1H)-one, quinazolin-4(3H)-one or quinazolin-2,4(1H, 3H)-one, respectively. The chemical structure of quinazolinones constitutes a crucial scaffold of natural and synthetic compounds with various therapeutic and biological activities. Quinazolinones are first synthesized by Stefan Niementowski (1866–1925) and named after Niementowski quinazolinone synthesis. Quinazolinones have strongly attracted the interest of medicinal chemist as they constitute a large class of compounds that exhibited broad spectrum of biological activities including antimicrobial, antimalarial, anticonvulsant, anticancer, antileishmanial, anti-inflammatory, etc. This chapter provides a brief overview on the recent advances on chemical and pharmacological aspects of quinazolinone derivatives published in the last decade.

**Keywords:** quinazolinones, antimicrobial, antimalarial, anticancer

#### **1. Introduction**

Heterocyclic compounds are organic cyclic compounds having at least one atom other than carbon in their ring structures. Quinazolinones are formed by fusion of benzene ring with 2-pyrimidinone (1), 4-pyrimidinone (2) or 2,4-pyrimidinedione (3) ring, and are named as quinazolin-2(*1H*)-one, quinazolin-4(*3H*)-one or quinazolin-2,4(*1H, 3H*)-one, respectively (**Figure 1**).

Quinazolinones are pharmacophoric scaffold ubiquitous in various biologically active natural products, synthetic compounds, pharmaceutical drugs, agrochemicals and veterinary products [1]. The chemical structure of quinazolinones constitute a crucial scaffold of compounds with various therapeutic and biological activities such as antimalarial [2], antimicrobial [3, 4], antitubercular [5], anticonvulsant [6], anticancer [7], antihypertensive [8], anti-diabetic [9], anti-inflammatory [10], anti-cholinesterase [11], cellular phosphorylation inhibition [12], dihydrofolate reductase inhibition [13], kinase inhibitory activities [14], inhibitors of tubuline polymerization [15], diuretic [16], antipsychotic [17], dopamine agonists [18] and anti-HIV [19]. Quinazolinones (**Figure 1**) is a core scaffold for the structure of more than 200 naturally occurring alkaloids isolated from different plant families and from various microorganisms such as *Bacillus cereus, Peganum nigellastrum, Dichroa febrifuga and Bouchardatia neurococca* [20]*.* Depending on the position of the keto group, they can be classified into three types. Among the 2(1H)-quinazolinones (**1**), 4(3H)-quinazolinones

**Figure 1.** *Quinazolinone and quinazolinedione structures.*

and 2,4(1H,3H)-quinazolinediones (**2**), 4(3H)-quinazolinones (**3**) are most prevalent and significant in medicinal chemistry possessing a multitude of pharmacological actions [21]. Quinazolinones are generally classified into four classes, 2-substituted quinazolinones, 3-substituted quinazolinones, 2,3-disubstituted quinazolinones and quinazolinone derivatives including fused quinazolinones [22].
