In silico analysis of cytotoxicity, rate of absorption and molecular docking of natural products against protease, integrase and HIV-1 reverse transcriptase

Abstract

AIDS is an infectious disease characterized by compromised defense cells, is caused by Human Immunodeficiency Virus -HIV, which affects about 36.7 million people. In its viral multiplication process, HIV requires protease, integrase and reverse transcriptase which are important enzymes in the process. Many therapeutic alternatives in the anti-HIV treatment are in the inhibition of these enzymes, many researches are being directed towards the search of new inhibitors that present better pharmacological profiles. The use of natural products in anti-HIV research has been growing substantially, research groups are betting on these substances in an attempt to offer potent drugs with reduced side effects. The objective of this study was to carry out chemoinformatic studies using cytotoxicity risk prediction tools; prediction of absorption and molecular docking of natural products found in the database of chemical structures (ChEMBL) and literature. The interactions with the targets, the% ABS and cytotoxicological analysis were evaluated. 243 natural products and 18 anti-HIV drugs were analyzed. All molecules had their 3D structures optimized by the methods of mechanical molecules (MM+) and Semi-empirical methods (AM1) (RMS 0.1 kcal /Å.mol in 600 cycles) through HyperChemTM 8.0 software. Structures were imported into the software OSIRIS DataWarrior 4.3.7 for prediction of cytotoxicity risks and absorption rate was calculated based on TPSA. Finally, molecular docking was performed using the software Molegro Virtual Docker 6.0 to calculate the energies of interaction with the protease receptors (PDB ID: 1OHR; reverse transcriptase PDB ID: 1REV and integrase (PDB ID: 3WNH). Of the 243 molecules of natural products with anti-HIV activity, 7 were promising because they did not present cytotoxicity risks (mutagenicity, carcinogenicity, skin irritability and reproductive system effect), better MolDockScore energies for all targets studied simultaneously by varying the interaction energies binder-receptor of -209.47kJ.mol -1 at -60.20kJ.mol -1 and absorption rate (% ABS) between 34.26% and 90.24%.

In Silico Studies for Bioactive Proposal Against Human Retinoblastoma From 3,4,5-Trihydroxycinamic Acid Derivatives

“…The software CDK Descriptor Calculator v1.4.8 was used to generate the molecular descriptors. After this, the molecules were imported into the software OSIRIS DataWarrior 5.0 to estimate the risks of cytotoxicity based on four parameters: mutagenicity (MUT), carcinogenicity (CAR), toxic effect on the reproductive system (ESR) and skin irritability (IRR) [3,4,5,6].…”