Abstract
As part of our investigations to support the medicinal potential of Pontederia crassipes , an invasive water hyacinth plant, through the isolation of bioactive phytochemicals, we report the isolation and structural elucidation of two novel tetralin‐pentacyclic triterpenoid conjugates, designated Crassipeloyd A (A1‐10T) and Crassipeloyd B (WH‐E2), from the ethyl acetate fraction. Structurally, these compounds align more closely with pentacyclic friedelane‐type frameworks than with oleananes. Their structures were unambiguously elucidated using IR, 1 H, 13 C, and HSQC NMR spectroscopy, alongside mass spectrometry. To explore their therapeutic relevance, we performed computational predictions of pharmacokinetics and HIV‐1 inhibitory activity using density functional theory (DFT)–optimized structures and molecular docking simulations. The HIV‐1 inhibitory profiles were conducted based on the structure–activity relationships of typical tetralin and pentacyclic triterpenoid derivatives. The in silico assessment predicted that compound A1‐10T exhibited the strongest binding affinity to HIV integrase (−8.5 kcal/mol), closely followed by WH‐E2 (−8.1 kcal/mol). These values compared favorably with reference inhibitors dolutegravir (−7.3 kcal/mol) and ritonavir (−7.0 kcal/mol). Meanwhile, ADMET modeling further suggested acceptable pharmacokinetic properties and low predicted systemic toxicity. These findings highlight A1‐10T and WH‐E2 as promising scaffolds with computationally predicted HIV‐1 inhibition. Importantly, the results represent theoretical models rather than experimental confirmation, warranting further experimental investigation into their potential use in treating HIV‐1 conditions and safety.