ARTICLE Antitumor, cytotoxic, and antioxidant evaluation of six heterocyclic compounds containing different heterocycle moieties Tasneem Mokhtar Radwan 1 | Maher Abdel-Aziz El-Hashash 2 | Ashraf Abdel-Hamid Farouk Wasfy 1 | Suzan Abdelhalim Abdallah 3 1 Chemistry Department, Faculty of Science, Benha University, Benha, Egypt 2 Chemistry Department, Faculty of Science, Ain-Shams University, Cairo, Egypt 3 Botany and Microbiology Department, Faculty of Science, Benha University, Benha, Egypt Correspondence Tasneem Mokhtar Radwan, Chemistry Department, Faculty of Science, Benha University, Benha, Qalyubia, Egypt. Email: tasneemmokhatar@gmail.com Abstract Heterocyclic compounds with different heterocycle moieties, namely ben- zoxazinone, benzimidazole, quinazolinone, and benzofuranone heterocyclic rings, were synthesized, characterized, and evaluated for their anticancer activ- ity against human hepatocellular carcinoma cell line (HepG2) using sul- forhodamine B (SRB) and dimethylthiazol-diphenyltetrazolium bromide (MTT) assays. Also, their cytotoxic activities were tested against human epithe- lioid carcinoma (Hela) cell line in comparison with normal cell, amniotic epi- thelial (WISH) cell line, as an in vitro toxicity estimation model. The results showed clearly that 2-(2-benzyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide 4 is the most potent antioxidant and anticancer agents. Although, 3-amino-2-ben- zylquinazolin-4(3H)-one 5 is less potent anticancer agent against Hela but it is more safe against normal cell (WISH). 1 | INTRODUCTION Cancer is moving to be a significant health problem in the world. [1–3] According to a World Health Organization (WHO) report, cancer is the second leading cause of death globally and is responsible for an estimated 9.6 mil- lion deaths in 2018. [4] Globally, about one in six deaths is due to cancer. [4] The mortality rate of patients is 782 000 deaths for liver cancer. [4] Cervical cancer is the fourth most frequent cancer in women with an estimated 570 000 new cases in 2018 representing 6.6% of all female cancers. Approximately 90% of deaths from cervical can- cer occurred in low- and middle-income countries. [5] For the in vitro chemosensitivity testing of tumor cell lines, several rapid calorimetric assays have been described. The tetrazolium (MTT) test was the most com- monly used in latest years. [6] The colorimetric test for MTT (dimethylthiazol-diphenyltetrazolium bromide) is based on mitochondrial uptake and succinate dehydroge- nase reduction of soluble, yellow, MTT tetrazolium salt to an insoluble blue MTT formazan product. [7] In con- trast, colorimetric assay for the sulforhodamine B (SRB) is based on the ability of the SRB dye to bind basic amino acid residues on proteins. [7] Several of the present treatments have problems with toxicity and drug-resistance, these encouraged researchers to explore effective new treatments for cancer disease. [8] Consequently, synthesis of new bioactive compounds such as heterocyclic compounds is an important aim for many researchers. Heterocyclic compounds have an active role as antibacterial, antiviral, antifungal, anti-inflammatory, and antitumor drugs. [9] For example, benzoxazinone deriv- atives are biologically interesting and they are now receiv- ing considerable attention due to their applications in medicine use for antifungal, antiviral, antibacterial, antima- larial, antipyretic, anticancer, and anti-HIV (human immu- nodeficiency virus) activities. [10] Moreover, 4H- 3,1-benzoxazin-4-one derivatives are shown to be inhibitors of α-chymotrypsin [11] and rhomboid proteases. [12] They consist of six-membered ring containing oxygen and Received: 2 October 2019 Revised: 8 November 2019 Accepted: 19 November 2019 DOI: 10.1002/jhet.3847 J Heterocycl Chem. 2020;1–12. wileyonlinelibrary.com/journal/jhet © 2020 Wiley Periodicals, Inc. 1