323 © 2024 The Author(s). Published by College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License Ibn Al-Haitham Journal for Pure and Applied Sciences Journal homepage: jih.uobaghdad.edu.iq PISSN: 1609-4042, EISSN: 2521-3407 IHJPAS. 2024, 37(4) A Brief Review of Phenolic Antioxidant and their Biological Activity Raied Mustafa Shakir1,* , Husam Salman Jasim2 and Shaimaa Abed Saoud3 1,2,3Department of Chemistry, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Baghdad, Iraq. *Corresponding Author. Received: 14 February 2023 Accepted: 28 August 2023 Published: 20 October 2024 doi.org/10.30526/37.4.3287 Abstract Antioxidant compounds are considered essential materials because they prevent or reduce free radical side chain reactions, which cause much damage. It is widely acknowledged that these damages are a major contributing factor to numerous diseases. Phenolic antioxidants are considered one of the most important antioxidant species. There is ample evidence that the antioxidant substances found in fruits and vegetables can prevent various diseases such as cancer, heart disease, diabetes, and cataracts. The food and pharmaceutical industries also make extensive use of it. Additionally, quite several phenolic medicinal compounds for anticancer, anti-inflammatory, anti-necrotic, hepato-protective, and neuroprotective purposes possess antioxidant abilities. The synthetic phenolic compounds exhibited remarkable antioxidant capacity in addition to various biological activities. These facts prompted the researchers to focus on newly synthesized phenolic compound derivatives and explore their biological activities, particularly those containing heterocyclics in their molecular structures. The biological activities of heterocyclic compounds are widely recognized. Keywords: Antioxidant, biological activity, heterocyclic, phenolic compounds, reactive oxygen species, synthetic compounds. 1. Introduction Free radicals, as well as the ROS (reactive oxygen species), are well known as extremely harmful molecules; moreover, they are believed to be the main source of much impairment in proteins, lipids, DNA, and carbohydrates [1]. A large number of illnesses were caused by the existence of free radicals, such as cancer [2], inflammation [3], degenerative diseases, and chronic diseases [4]. Antioxidant compounds are significant because they can prevent any damage that free radicals may cause. Furthermore, many researchers have emphasized that anti- inflammatory medicines and anticancer drugs possess antioxidant abilities [5]. There are two major types of antioxidants. The first one is the natural antioxidant, and the second type is the synthetic antioxidant, as demonstrated in Figures 1 and 2. The antioxidant compounds usually share common structure features that account for their antioxidant properties, such as the existence of a multi-phenol group as in polyphenols and flavonoids, long-range conjugation as in α-tocotrienol (vit E) [6], and the existence of a steric hindrance phenolic group [7, 8]. https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0003-2668-2305 mailto:raiedalsayab@yahoo.co.uk https://orcid.org/0000-0002-0453-8567 mailto:husam_alaythawy78@yahoo.com https://orcid.org/0000-0002-0782-1296 mailto:shaimaachem@hotmail.com IHJPAS. 2024, 37(4 ) 324 Two mechanisms can be used by the antioxidant substrates to delay or prevent the propagation reaction of the free radical. The first mechanism is known as hydrogen-atom transfer (HAT) [9], as demonstrated in lipid peroxidation, as shown in Scheme 1. The next mechanism recognized is single electron transfer (SET) [10], as presented in Scheme 2. Phenolic compounds are considered one of the most important antioxidant materials. This work will present the most significant phenolic antioxidant compounds. The compound coded as AO-60, as in Figure 3 is commonly used to protect rubber from oxidation in commercial settings [11]. Numerous phenolic compounds have demonstrated therapeutic and diverse biological activity. For instance, researchers proved compound R-830 to be a potent inhibitor of guinea pig lung lipoxygenases and an efficient anti-inflammatory drug [12]. The compound coded E-5110 is recognized for its medicinal uses as a non-steroidal anti-inflammatory agent [13], while KME-4 in Figure 4 is recognized for its analgesic capability besides its anti-inflammatory properties [14]. Table 1 illustrates the significant antioxidant and various biological activities of several di-tert-butyl phenols attached to heterocyclics. 2. Materials and Methods 2.1 Synthesized phenolic derivative The 5-Aryl Oxadiazole derivatives containing di-tert-butyl phenol were synthesized, and their antioxidant capability was screened utilizing DPPH and FRAP assays. This study found the type and position of the substituted group at the aryl group play a significant role in enhancing or minimizing the antioxidant ability [23], as depicted in Figure 5. 3. Results and Discussion The synthesized 1,3,4-oxadiazole ring derivatives at position six of the 2-methyl phenol are illustrated in Figure 6. This work tested the antioxidant and antibacterial activity of these compounds. This study concluded an inverse relationship between increasing the antioxidant ability and the antibacterial capacity [24]. Figure 7 shows the synthesis of hydro-pyrimidine, a compound with a multi-phenol group. These compounds presented antibacterial activity in addition to their significant antioxidant ability. Furthermore, the simulation study of these compounds exhibited potential inhibitors of the gyrase enzyme [25]. The fused triazole of 2-methyl phenol derivatives, shown in Figure 8 exhibits significant antioxidant activity. In addition to exhibiting considerable antioxidant activity, these compounds demonstrated potent tubulin inhibitors when compared to colchicine as a reference [26]. Bromo Phenolic derivatives were synthesisied as new sagnificant antioixdant capacity [27] as depicted in Figure 9. Phenolic thiazolidine-2,4-dione derivatives were synthesized and investigated for their antioxidant ability using a fragment assay, a phosphomolybdate assay for total antioxidant capacity (TAC), a reducing power assay (RP), and the bond dissociation energy [28]. This study found that the number of hydroxyl groups and O-alkyls play an important role in enhancing antioxidant ability in Figure 10. New phenolic derivatives containing imidazole rings in Figure 11 were synthesized. These compounds exhibited remarkable antioxidant activity [29]. The 2,6-bis-(1,1-dimethylethyl) phenol derivatives in Figure 12 were synthesized. These compounds exhibited a noteworthy anti-inflammatory capacity [30]. IHJPAS. 2024, 37(4 ) 325 Table 1. Some phenolic antioxidant and biological activities. No Structure Biological activity Reference 1 NFkB inhibitor for treating cancers [15] 2 anticancer [16] 3 antidiabetic activity [17] 4 anti-inflammatory [18] 5 antibacterial [19] 6 antifungal [20] 7 Gastroprotective Activity [21] IHJPAS. 2024, 37(4 ) 326 8 anti-inflammatory drugs (Darbufelone) [22] Figure 1. Some natural phenolic compounds in plants and fruits. Figure 2. Some synthetic phenolic compounds. IHJPAS. 2024, 37(4 ) 327 Scheme 1. Rote of HAT mechanism. Scheme 2. Rote of SET mechanism. Figure 3. The AO-60 compound. Figure 4. Structure of R-830, E-5110, KME-4. IHJPAS. 2024, 37(4 ) 328 Figure 5. Synthesized rote of 5-Aryl Oxadiazole derivative as antioxidant. Figure 6. Synthesis rote of 2-methylphenol derivative as promising antioxidant and antibacterial. Figure 7. Hydro-pyrimidine moiety of multi phenol. IHJPAS. 2024, 37(4 ) 329 Figure 8. Rote of synthesis fused triazole containing phenol as tubulin inhibitor. Figure 9. Bromophenol derivative as significant antioxidant. Figure 10. Synthetic phenolic thiazolidine-2,4-dione derivatives. Compound R1 R2 R3 R4 4a 5a H H OH H 4b 5b H OH H H 4c 5c H OCH3 OH H 4d 5d OH H H H 4e 5e H OH OCH3 H 4f 5f OH OH H H 4g 5g OH H H Br 4h 5h H OCH2CH3 OH H 4i 5i OH OCH2CH3 H H 4j 5j H OCH3 OH OCH3 4k 5k OH H OH H 4l 5l H OH OH H IHJPAS. 2024, 37(4 ) 330 Figure 11. Imidazole derivative consist phenol. Figure 12. Phenolic derivatives exhibited anti-inflammatory capacity. 4. Conclusion Natural phenolic compounds gain important attention due to their widespread existence in plants. especially those that exhibit pharmaceutical effects. The synthetic phenolic compound also received serious attention from researchers due to its significant antioxidant ability and various biological activities. Phenolic derivatives containing heterocyclics gain most attention due to their significant biological activity besides their antioxidant abilities. Acknowledgment The authors thank the University of Baghdad/ College of Education for Pure Science (Ibn Al-Haitham) for approving this work. Conflict of Interest The authors declare there are no conflicts of interest. All authors alone are accountable for the content and writing of the paper. Funding There is no financial support. Ethical Clearance This work has been approved by the Scientific Committee at the University of Baghdad/ College of Education for Pure Science (Ibn Al-Haitham). IHJPAS. 2024, 37(4 ) 331 References 1. 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