Computational strategies to explore antimalarial thiazine alkaloid lead compounds based on an australian marine sponge plakortis lita
| Title | Computational strategies to explore antimalarial thiazine alkaloid lead compounds based on an australian marine sponge plakortis lita |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Lilly, A, Jisha, RS, Masand, VH, Gajbhiye, JM, Shibi, IG |
| Journal | Journal of biomolecular Structure & Dynamics |
| Volume | 35 |
| Issue | 11 |
| Pagination | 2407-2429 |
| Date Published | AUG |
| Type of Article | Article |
| Abstract | In this work, an attempt was made to propose new leads based on the natural scaffold Thiaplakortone-A active against malaria. The 2D QSAR studies suggested that three descriptors correlate with the anti-malarial activity with an R2 value of 0.814. Robustness, reliability and predictive power of the model were tested by internal validation, external validation, Y-scrambling and Applicability domain analysis. HQSAR studies were carried out as an additional tool to find the sub-structural fingerprints. The CoMFA and CoMSIA models gave Q2 values of 0.813 and 0.647, and R2ncv values of 0.994 and 0.984, respectively. Using the 2D-QSAR equation, the activity values of the seven modified compounds were calculated and it was found that three molecules showed good anti-malarial activity. Molecular docking of the 42 Thiaplakortone-A derivatives with P. falciparum calcium-dependent protein kinase 1 (PfCDPK1) was carried out to find out protein-ligand interactions. Data mining of the bioassay dataset AID: 504850 using the classifier based on Random Forest (RF) of Weka suggested that all of the eight molecules selected and three out of the seven virtual molecules were anti-malarial active. Both the virtual molecules and drug molecules were docked with CYP3A4, indicating that the virtual molecules could metabolize easily. Toxicity studies using Osiris shows that three molecules showed no toxic characters. |
| DOI | 10.1080/07391102.2016.1220870 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 2.3 |
Divison category:
Organic Chemistry
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