**Abstract**

Free radical-induced changes in cellular and organ levels have been studied as a possible underlying cause of various adverse health conditions. Important research efforts have, therefore, been made to discover more powerful and potent antioxidants/free radical scavengers for the treatment of these adverse conditions. The phytoestrogen coumestrol intensively attracted scientific interest due to their efficient pharmacological activities. In this scenario, DFT studies were carried out to test the antiradical activities of coumestrol and its derivatives. The results obtained from FEDAM plots demonstrated that the coumestrol derivatives pointed out were good radical scavengers relative to the parent molecule in the gas phase. The derivatives whose 16thposition substituted with electron-donating groups like -NH2, -OCH3 and -CH3 showed good antioxidant capacity. Three antioxidant mechanisms, including hydrogen atom transfer (HAT), electron transfer followed by proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET), were investigated by measuring thermodynamic parameters.

**Keywords:** phytochemical, coumestrol, anti-oxidant activity, global descriptive parameters, donor acceptor map, full electron donor acceptor map

#### **1. Introduction**

Extreme production of free radicals such as reactive oxygen species (ROS), reactive nitrogen species (RNS) and reactive sulphur species (RSS) with half-lives of just a few nanoseconds is the source of the harmful process called oxidative stress, the effects of which can significantly alter cell structures (e.g. membranes) and destroy bio molecules such as lipids, lipoproteins, proteins, and nuclei [1–3]. Our body has natural defence mechanisms provided by secondary metabolites called antioxidants to neutralise these ROSs. In the respiratory chain, the electron transfer to molecular oxygen takes place and the electron transport chain is located on the mitochondria, suggesting that the ROS is mainly formed in mitochondria [4]. Natural products reflect a diverse community of different kinds of antioxidants that inhibit or postpone the oxidation of essential cell macromolecules by scavenging certain free radicals [5, 6]. Antioxidants are commonly dispersed in different parts of plants, such as fruits, leaves, flowers, etc., and cow milk and honey milk contain a number of antioxidants [7–9].

Various antioxidant techniques have involved either the increase of endogenous antioxidant enzyme defences (e.g., superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase) or the enhancement of non-enzymatic defences (e.g., glutathione, vitamins) by dietary or pharmacological means in order to counteract and neutralise the deleterious effects of ROS/RNS. By scavenging free radicals and decreasing oxidative stress, antioxidants may slow, inhibit or prevent the oxidation of oxidizable substrates. The defence against ROS is, however, impaired or harmed in disease conditions and the oxidant load increases. Under such circumstances, the external supply of antioxidants is sufficient to mitigate the adverse effects of oxidative stress [10]. It is generally recognised that the presence of one or more conjugated -OH groups or -COOH groups, which increases the capacity of such a molecule to quench free radicals, is the most important structural feature that facilitates successful antioxidant activity. Therefore Studies have shown that polyphenols (both natural and synthetic) are promising antioxidants [5, 6].

Coumestrol is a phytoestrogen belongs to the coumestan family of compounds, in plants. Coumestrol exhibit estrogenic and antiestrogenic activity based on oestrogen levels in the body. It has a similar structure to isoflavones and estradiol. It was first isolated from ladino clover in 1956 by E.M. Bickoff. Coumestrol is widely distributed in plants like clover, alfalfa, soya beans, peas, brussels sprouts, spinach, strawberries and a variety of legumes. Coumestrol can easily pass through cell membranes due to its low molecular weight and stable structure. Coumestrol exhibit a neuroprotective effect via cerebral ischemia prevention. Coumestrol exert beneficial effects in cancer, menopause, osteoporosis, atherosclerosis, and cardiovascular disease. In addition to this, coumestrol shows Anti-ageing, Neuroprotective, Anti-adipogenic, Depigmenting activity, Anti-oxidant and Anticancer properties. A detailed mechanistic (radical scavenging mechanism) study on coumestrol and its derivatives is needed to describe the antioxidant characteristics in a satisfactory manner, so the current work is an attempt to provide a theoretical exploration of the antioxidant property of the molecules under study.

### **2. Materials and methods**

#### **2.1 Materials**

The present study mainly focussed on the anti-oxidant property of coumestrol and its derivatives. The three-dimensional structure of the parent molecule is downloaded from the PubChem database. Using the Gaussview-5.0 graphical user interface, the input structures of coumestrol derivatives were drawn and assigned to the Gaussian 09 software package for computational calculations.

#### **2.2 Computational methodology**

#### *2.2.1 Frontier molecular orbital (FMO) analysis*

In particular, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) form the frontier molecular orbitals (FMOs). FMOs are strongly involved in the study of the electrical and chemical properties of substrates. Analysis of frontier molecular orbitals of coumestrol and its derivatives have been carried using density functional theory and their energy gaps were computed. A lower energy gap indicates the reactivity of the molecule. An anti-oxidant 's working mechanisms are derived from HOMO, as a weak electron donor represents a lower HOMO, and vice versa. In addition, electron transfer is

*Theoretical Studies on Anti-Oxidant Activity of the Phytochemical, Coumestrol and Its… DOI: http://dx.doi.org/10.5772/intechopen.96967*

involved in hydrogen abstraction, and therefore the study of HOMO-LUMO is important.
