Computational toxicology and food safety assessment of Parkia timoriana phytoconstituents using quantitative structure-activity relationship (QSAR) modeling approaches

Abstract

As a lead compound, natural compounds have undergone extensive research in different enterprises. Since they might also have other adverse effects, determining their toxicity is crucial. Computational methods can circumvent the main challenges associated with assessing the toxicity of substances using in vivo and in vitro techniques, including time, money, labor, and the use of animal models. Although Parkia timoriana (PT) has a significant economic potential, its exploitation has yet to be thoroughly explored in terms of its toxicity and food safety. In PT seed pod extracts, 61 phytocompounds with a predominance of alkaloids, flavonoids, and terpenoids were identified using GC-MS and LC-MS/MS analysis. Utilizing the TEST, OECD QSAR toolkit, VEGA-HUB, Toxtree, and PASS tools, phytocompounds from PT were assessed for toxicity, food safety risk assessment, and biological activity. The phytochemicals were tested on multiple species, including Daphnia magna, Pimephales promelas, Tetrahymena pyriformis, and rats, to determine their toxicity using the QSAR-TEST tool. For aquatic and mammalian organisms, the phytocompounds from PT were shown to be hazardous in the following four hierarchical orders: i) P. promelas>T. pyriformis>D. magna>R. norvegicus, ii) P. promelas>D. magna>T. pyriformis>R. norvegicus, iii) D. magna>
P. promelas>T. pyriformis>R. norvegicus, and T. pyriformis>P. promelas>D. magna>R. norvegicus. Despite being non-bioaccumulative, non-mutagenic, and non-carcinogenic in nature, the majority of phytocompounds were developmental toxins. More than half of the phytochemicals derived from PT were highly toxic (Cramer oral toxicity) and manifested negative side effects (with a lower NOAEL value).Most of the substances did not exhibit organ toxicity in the repeated dose toxicity test, were bioavailable, metabolized by cytochrome-P450 pathway, and were excreted from the body. PASS predicted that the examined phytoconstituents from PT were to demonstrate a wide range of anti-oxidant, free radical scavenger, anti-inflammatory, antiviral, anti-fungal, anti-neoplastic, antibacterial, and anti-protozoal activities. For the purpose of exploring drug discovery, additional research of the phytocompounds on in vivo models is advised.