Abstract

THROMBOLYTIC EFFECT OF TREMA ORIENTALIS AND PASS PREDICTION, MOLECULAR DOCKING, ADME/T PROPERTY ANALYSIS OF ITS ISOLATED COMPOUNDS.

Mohammad Shah Hafez Kabir*, Md. Saiful Islam Arman, Sumya Afroze, Md. Shohel Hossain, Fahmida Abdullah Tuly, Mosarrof Hossain, Md. Najem Uddin, Hosna Banu, Md. Mominur Rahman

Abstract

The present study aims to investigate the thrombolytic effect of ethanol extract of Tremas orientalis leaves by in vitro clot lysis method and in silico PASS prediction and molecular docking used for eight phytoconstituents namely (-)-ampelopsin f, (+)-catechin, (+)- syringaresinol, (-)-epicatechin, hexacosanoic acid, N-(trans-pcoumaroyl) tyramine, simiarenone and trans-4-hydroxycinnamic acid isolated from T. orientalis, to identify whether these compounds interact with the responsible protein (tissue-type plasminogen activator). And also ADME/T properties of the phytoconstituents were analyzed using Qikprop 3.2 module. In vitro clot lysis model was used to observe the thrombolytic effect of the extract, where it exhibited 52.38 ± 2.45% clot lysis. In the PASS prediction for their thrombolytic activity of the isolated phytoconstituents, we found wide range of activity. A wide range of docking score found during molecular docking by CPI server. (-)-ampelopsin f, (+)-catechin, (+)-syringaresinol, (-)-epicatechin, hexacosanoic acid, N-(trans-p-coumaroyl) tyramine, simiarenone and trans-4-hydroxycinnamic acid showed the docking score -8.6, -7.4, -7.6, - 7.2, 5.5, -8.6, -8.2, -6.1, respectively. Both in silico models showed similar value for the same compound, because (-)-ampelopsin f showed high value in both in silico models. All the data support that (-)-ampelopsin f is the best compounds for thrombosis management, as it possessed higher value both in PASS prediction and Molecular docking. After (-)-ampelopsin f, N-(trans-p-coumaroyl) tyramine may be the second choice. So, (-)-ampelopsin f and N- (trans-p-coumaroyl) tyramine may be competitive candidate for promising thrombolytic agent. From the ADME profiles of (-)-ampelopsin f and N-(trans-p-coumaroyl) tyramine, it cleared that they might safe for human. Further in vivo investigation need to identify whether (-)-ampelopsin f, N-(trans-p-coumaroyl) tyramine and other compounds have thrombolytic effect or not.

Keywords: Trema orientalis, PASS prediction, Molecular docking, ADME/T properties.