Novel Quinazolines Bearing 1,3,4-thiadiazole-aryl Urea Derivative As Anticancer Agents: Design, Synthesis, Molecular Docking, DFT and Bioactivity Evaluations

Overview

Journal BMC Chem

Publisher Springer Nature

Specialty Chemistry

Date 2024 Feb 12

PMID 38347613

Authors

Sara Masoudinia

Marjaneh Samadizadeh

Maliheh Safavi

Hamid Reza Bijanzadeh

Alireza Foroumadi

Affiliations

Soon will be listed here.

Abstract

A novel series of 1-(5-((6-nitroquinazoline-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives 8 were designed and synthesized to evaluate their cytotoxic potencies. The structures of these obtained compounds were thoroughly characterized by IR, H, and C NMR, MASS spectroscopy and elemental analysis methods. Additionally, their in vitro anticancer activities were investigated using the MTT assay against A549 (human lung cancer), MDA-MB231 (human triple-negative breast cancer), and MCF7 (human hormone-dependent breast cancer). Etoposide was used as a reference marketed drug for comparison. Among the compounds tested, compounds 8b and 8c demonstrated acceptable antiproliferative activity, particularly against MCF7 cells. Considering the potential VEGFR-2 inhibitor potency of these compounds, a molecular docking study was performed for the most potent compound, 8c, to determine its probable interactions. Furthermore, computational investigations, including molecular dynamics, frontier molecular orbital analysis, Fukui reactivity descriptor, electrostatic potential surface, and in silico ADME evaluation for all compounds were performed to illustrate the structure-activity relationship (SAR).

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