β-Enaminonitrile in the Synthesis of Tetrahydrobenzo[]thiophene Candidates with DFT Simulation, Antiproliferative Assessment, Molecular Docking, and Modeling Pharmacokinetics

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Jun 11

PMID 38860247

Authors

Amna S Elgubbi

Eman A E El-Helw

Motaleb S Abousiksaka

Abdullah Y A Alzahrani

Sayed K Ramadan

Affiliations

Soon will be listed here.

Abstract

Among sulfur-including heterocycles, the benzothiophene skeleton is one of the worthy structure fragments that exhibit structural similarities with active substrates to develop various potent lead molecules in drug design. Thus, some tetrahydrobenzo[]thiophene candidates were prepared from the β-enaminonitrile scaffold reactions with diverse carbon-centered electrophilic reagents and supported with DFT studies. The antiproliferative effect was screened against MCF7 and HePG2 cancer cell lines, and the results displayed the highest potency of imide 5, Schiff base 11, and phthalimido 12 candidates. A molecular docking study was operated to explore the probable binding modes of interaction, and the results revealed the good binding affinity of compounds 5, 11, and 12 toward the tubulin protein (PDB ID 5NM5) with respect to paclitaxel (a tubulin inhibitor) and co-crystallized ligand (GTP). Besides, modeling pharmacokinetics analyses displayed their desirable drug-likeness and bioavailability properties.

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