Cancer, a highly life-threatening disease is manifested by its proficient proliferation rather than normal cells which arises because of multiple factors as faulty cell division, damage to the DNA structure, genetic alterations. Histone, the basic component of chromatin is regulated by two antagonistic enzymes like histone deacetylase (HDAC) and histone acetyl transferase (HAT). Different classes of HDACs have been evolved as an appealing target for therapeutic candidates in several human cancers due to its ubiquitous mutation and unusual expression in various human diseases, specifically cancer (Barneda zahonero and Parra, 2012). One of the ultimate breakthroughs in the pharmaceutical sectors is the quest and exploration of molecules as histone deacetylase inhibitors (HDACi) to function as effective anticancer drugs. Recently plant derived compounds showed promising HDAC inhibitory activity due to its antiproliferative effect and the potential to induce apoptosis (Senawong et al., 2013).
Plants in general possess a class of approximately 4000 kinds of naturally existing polyphenolic substances known as flavonoids. Vegetables, fruits, seeds, nuts, spices, flowers, stems and red wine are the rich sources of flavonoids (Nayaka et al., 2014). The metabolism of acetate and shikimic acid pathways yield a C6-C3-C6 chemical skeleton composed of heterocyclic benzopyran with oxygen and two rings of aromatic molecules commonly known as flavonoids. It is widely acknowledged that flavonoids have plenty of implications in several physiological pathways. (Filho et al., 2015). One of the most ubiquitously distributed and extensively studied flavonoids is apigenin. The primary sources of this substance are Asteraceae plants, specifically those in the genera Achillea, Matricaria, Artemisia and Tanacetum. Chamomile, made from the withered flowers of Matricaria chamomilla, serves as one of the foremost prominent sources of apigenin (Salehi et al., 2019).
Based on the research findings, it is speculated that only eight percent of drug compounds which undergo clinical trials have the likelihood to be commercialised, whereas 20% of the drugs breakdown in the later phases of drug discovery owing to their toxicity as the core factor (Drwal et al., 2014). The most dreadful toxicological implications posing threat to human health are the carcinogenicity and mutagenicity. Testing on animals are an essential milestone for assessing the probable lethality of newly developed drugs and cosmetics. In silico prediction approaches provide an alternate option to elucidate the preclinical drug discovery process and also it has an advantage as minimizing the time, expenditure, and testing on animals that are involved (Arulanandam et al., 2022). Toxicological risk assessment is progressively being executed by computer-based (in silico) forecasting, yet there remains a bit of scepticism about these approaches. In silico techniques now afford valuable incentives to both legislative standards and criteria for risk evaluations, facilitating the pharmaceutical sector to review the risk and safety picture of a compound. This has been made achievable by breakthroughs in the discipline of algorithmic computing. Hence in this study, apigenin as HDAC inhibitor and its toxicity predictions are carried out using various computational in silico models.