ABSTRACT
The delivery of a premature neonate may have significant emotional and financial consequences to families, with consequential implications for public-sector services, and is a serious clinical concern linked with perinatal death, severe neonatal morbidity, and moderate to severe juvenile impairment. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat acute preterm labor, tocolysis with these drugs does not result in a pregnancy extension of more than two days. This research aims to discover new tocolytic chemicals in plants traditionally used to treat premature labor.
The phyto-constituents of five plants used traditionally for preterm labor were obtained from literature sources; the leaves of Alchornea laxiflora (15), the root stem and bark of Ricinodendron heudelotii (21), the calyx of Hibiscus sabdariffa (40), the leaf of Carica papaya (72), and fruit of Piper guineense (93). Their 3D SDF structures were obtained from PubChem and docked against a Cyclo-oxygenase protein (5KIR) with Pyrx using rofecoxib and celecoxib as the standard drugs after the protein was processed by Chimera. Post-docking analysis, ADME, and toxicity properties was done with Biodiscovery Studio, SwissADME and admetSAR online servers respectively. Their toxicity classes and lethal dose, 50%, was obtained using PROTOX-II online server.
The drug-like and lead-like compounds obtained from the phyto-constituents of these plants after computational analysis are, Quercetin (Pubchem ID 5280343) from Alchornea laxiflora (Euphorbiaceae), (+)- Gallocatechin (PID 65084), 3’, 4’ Dihydroflavonol (PID 145826) ,and Isorhamnetin (PID 5281654), from Rinodendron heudelotti (Euphorbiaceae), 3-hydroxycoumarin (PID 13650) ), and Delphinidin (PID 128853), from Hibiscus sabdariffa (Malvaceae), Limetin (PID 2775) and Riboflavin (PID 493570) from Carica papaya (Cariceae), and Piperidine (PID 54930) from Piper guineense (Piperaceae), nine (9) lead compounds altogether. They all had good binding affinities with the active site (TYR A-385) of the receptor protein (5KIR) responsible for the cyclooxygenase activity of the receptor, with the highest being 3’,4’ Dihydroflavonol which had a binding affinity of -7.6 Kcal/mol. The nine (9) lead compounds had good ADMET profiles relative to the standard drugs. Wet laboratory experimentation will be required to further validate the results of this in-silico study, but it is possible that these molecules could offer tocolytic benefits in the management of preterm labor. This optimization could be used to alter the ADMET properties of these molecules while retaining their biological activities.
