Croton's therapeutic promise: A review of its phytochemistry and critical computational ADME/Tox analysis

Abstract

The genus Croton (Euphorbiaceae family) is constituted of approximately 1300 species with remarkable ethnomedicinal backgrounds supported by extensive pharmacological studies alongside over 900 compounds associated with some of the activities. However, there is no systematic review of the compounds' physicochemical features in tandem with their absorption, distribution, metabolism, extraction, and toxicity (ADMET) to corroborate both ethnomedicinal and pharmacological potential. This study focused on a virtual analysis of the physicochemical-ADMET properties of compounds from the genus Croton reported between 1990 and 2024. Various electronic databases, namely Google, Google Scholar, Scopus, ScienceDirect, Biomed Central, and Pubmed, were used to search for information related to the chemistry and pharmacology of Croton species. The physicochemical, ADMET and Scaffold information of the reported croton compounds were obtained from SWISSADME, pKCSM, and Data Warrior webservers, which were then analyzed by Origin Pro 2023 statistical software. Diterpenoids (67.2 %), alkaloids (11.1 %), sesquiterpenes (4.7 %), flavonoids (3.2 %), other terpenoids (Sesterterpenoid and triterpenoids; 2.7 %), monoterpenoids (1.7 %), megastigmane glycosides (2.2 %), proanthocyanidins (0.8 %), and other assorted compounds (6.4 %) make up the total of 900 compounds reported among the genus Croton between 1990 and 2024. Based on principal component analysis (PCA) results (PC1 and PC2, with total variances of 43.79 % and 16.50 %, respectively), most of these compounds have the same chemical space as FDA-approved medications. The biological activity that was most frequently reported was cytotoxicity (52 %) followed by anti-inflammatory actions (13 %). After the ADME screening, 38 % of the Croton compounds met the predetermined criteria for drug-likeness while toxicity analysis cleared 35.487 %, as nontoxic. The primary appropriate therapeutic candidates identified by the post- ADMET analysis were clerodanes, kauranes, labdanes and abietanes compounds, with respective ratios of 10, 10, 10, and 5 %. Alkaloids (5 %), crotofolanes at 20 %, and sesquiterpene majorly at 40 % were too determined to be appropriate therapeutic candidates. The majority of these compounds are drug-like with recommended ADME/Tox profiles. Given the promising cytotoxic potential of compounds from the genus Croton, further studies are warranted to determine their therapeutic applications and optimize their pharmaceutical development.