Scheme 1.

The workflow of the method for identifying compounds with potential usefulness in VD. (A) Phase 1: Creating a phlebotonic reference dataset from MEDLINE, EMBASE, and Scopus databases from the information obtained up to March 2023. The complexheatmap (K-means) in R-Studio was used to cluster the reference compounds based on their molecular descriptors. (B) Phase 2: Selecting drug-like NPs and SMSs from multiple datasets based on the Quantitative Estimate of Drug-likeness (QED). The molecules were searched on the PubChem server to obtain their structural information. Data filtering of NPs and SMSs to obtain drug-like molecules by QED was searched for the reported targets in PubChem. (C) Phase 3: Using the Tanimoto coefficient and Ward’s clustering method to identify compounds with potential usefulness in VD by comparing fingerprints of drug-like NPs, SMSs, and reference compounds. (D) Phase 4: Using Cytoscape software version 3.8 to identify the best candidates with potential usefulness in VD through network analysis. (E) Phase 5: Experimental evaluation of NPs and SMSs in an in vivo model of acute venous hypertension.