Design, synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents

Giang Le-Nhat-Thuy; Thuy Van Dinh; Hai Pham-The; Hung Nguyen Quang; Nga Nguyen Thi; Tuyet Anh Dang Thi; Phuong Hoang Thi; Tu Anh Le Thi; Ha Thanh Nguyen; Phuong Nguyen Thanh; Trung Le Duc; Tuyen Van Nguyen

doi:10.1016/j.bmcl.2018.10.016

Design, synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents

Bioorg Med Chem Lett. 2018 Dec 15;28(23-24):3741-3747. doi: 10.1016/j.bmcl.2018.10.016. Epub 2018 Oct 11.

Authors

Affiliations

¹ Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
² Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
³ Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hoan Kiem, Hanoi, Viet Nam.
⁴ Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
⁵ Chu Van An High School, 10, Thuy Khue, Hanoi, Viet Nam.
⁶ Institute of Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: ngvtuyen@hotmail.com.

PMID: 30337229
DOI: 10.1016/j.bmcl.2018.10.016

Abstract

In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11-14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.

Keywords: 4-Anilinoquinazolines; Cytotoxic agents; EGFR inhibitors; Hybrids; Triazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Aniline Compounds / chemical synthesis
Aniline Compounds / chemistry*
Aniline Compounds / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Drug Design*
Drug Screening Assays, Antitumor
ErbB Receptors / chemistry
ErbB Receptors / metabolism
Humans
Molecular Docking Simulation
Neoplasms / drug therapy
Neoplasms / metabolism
Quinazolines / chemical synthesis
Quinazolines / chemistry*
Quinazolines / pharmacology*
Sequence Alignment
Structure-Activity Relationship
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacology*

Substances

Aniline Compounds
Antineoplastic Agents
Quinazolines
Triazoles
anilinoquinazoline
EGFR protein, human
ErbB Receptors