Cissus verticillata, a traditionally valued medicinal plant, was investigated for its phytochemical composition and therapeutic potential through integrated experimental and computational approaches. The plant material was authenticated, extracted with hydroalcoholic solvent, and subjected to organoleptic, physicochemical, microbial, and phytochemical analyses. The extract yield was 10.95%, appearing dark brown to greenish-brown with stable physicochemical parameters, near-neutral pH, and absence of microbial or heavy metal contamination. Preliminary phytochemical screening confirmed abundant flavonoids, phenolics, and alkaloids, with moderate tannins and saponins, highlighting strong antioxidant and anti-inflammatory potential. LC-HRMS profiling revealed a chemically diverse fingerprint, with seven major compounds tentatively identified: kaempferol-3-O-rutinoside, rutin, chlorogenic acid, luteolin-7-O-glucoside, procyanidin B2, a saponin derivative, and cinnamtannin A2. These metabolites represent key classes of flavonoids, phenolic acids, tannins, and saponins. Molecular docking against the HER2 enzyme (PDB ID: 3RCD) revealed promising binding affinities, with rutin (-10.3 kcal/mol), kaempferol-3-O-rutinoside (-10.2 kcal/mol), and luteolin-7-O-glucoside (-9.9 kcal/mol) surpassing the native ligand (-9.6 kcal/mol). These compounds formed multiple hydrogen bonds with residues such as MET801, ASP863, and ARG849, along with hydrophobic interactions that stabilized binding. Procyanidin B2 (-9.2 kcal/mol) and soyasaponin I (-9.1 kcal/mol) showed moderate affinity, while chlorogenic acid (-8.2 kcal/mol) and cinnamtannin A2 (-6.2 kcal/mol) exhibited lower activity. In silico ADMET predictions confirmed that chlorogenic acid, luteolin-7-O-glucoside, and kaempferol-3-O-rutinoside possessed superior drug-likeness, good absorption, minimal CYP450 interaction, and reduced toxicity compared to the native ligand. These findings support Cissus verticillata as a phytochemical-rich candidate for HER2-targeted therapeutic development.
Keywords: Cissus verticillata, LC-HRMS, phytoconstituents, HER2, molecular docking, ADMET.
How to cite this article: Saichandana C, Prasad PD. Exploring Cissus verticillata as a Source of HER2 Inhibitors: Phytochemical Profiling, Molecular Docking, and ADMET Analysis. Int J Drug Deliv Technol. 2025;15(4): 1514-1532, DOI: 10.25258/ijddt.15.4.8.