Table A2.
Summary of recent ligand-based QSAR modeling.
| Reference | Modeled Data | Descriptor Type | Algorithm | Validation Strategy | Application and Result |
|---|---|---|---|---|---|
| Gaikwad 2018 [25] | IC50 of 102 phenylindoles cytotoxic against MCF7 cancer cell line | Fragment-based holograms implemented in SYBYL-X (Certara) | PLS | Two sets were used: training (77) and test (25). Leave- one-out and five-fold cross-validation were used. | Analysis of literature data allowed the authors to highlight structural features important for cytotoxicity. |
| Extended connectivity fingerprints, physicochemical descriptors | Naïve Bayes (Discovery Studio 3.0, Accelrys) | ||||
| Guo 2020 [26] | 1076 diverse colchicine-site targeting small molecules extracted from the ChEMBL database | Extended-connectivity fingerprints, path-based fingerprints | Naïve Bayes | Five-fold cross-validation. | A colchicine site-binding inhibitor of tubulin polymerization was established after a virtual screening campaign. |
| Single Tree | |||||
| Random Forest | |||||
| Stefanski 2018 [27] | IC50 of 83 thio-derivatives of combretastatin-A4 mined from literature | Extended connectivity fingerprints, physicochemical descriptors | Naïve Bayes | Leave-one-out, cross-validation, and external test set methods. The external validation test set was composed of 20 tubulin inhibitors and 800 decoys. | Two virtual hits selected by consensus QSAR modeling were later confirmed to be cytotoxic due to perturbing microtubule polymerization by binding at the colchicine site. |
| Multiple Linear Regression | |||||
| Quan 2018 [28] | IC50 values of 64 literature-mined derivatives of combretastatin A-4 | CoMFA (steric and electrostatic fields) | PLS (SYBYL-X 2.0, Tripos) | Leave-one-out validation | A 3D QSAR study highlighted structural elements with pronounced relation to activity value, useful for further optimization. |
| CoMSIA (steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields) | |||||
| Pandit 2021 [29] | IC50 values of 49 tubulysin derivatives reported in the literature | CoMFA (steric and electrostatic fields) | PLS (SYBYL-X 2.0, Tripos) | Cross-validation | 3D QSAR investigation of structure-activity data on tubulysins lead to rational design and synthesis of a new class of cytotoxic in vitro tubulysin derivatives |
| CoMSIA (steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields) |