Synthesis and biological evaluation of novel benzo[a]pyridazino[3,4-c]phenazine derivatives

Giang Le-Nhat-Thuy; Tuyet Anh Dang Thi; Quynh Giang Nguyen Thi; Phuong Hoang Thi; Tuan Anh Nguyen; Ha Thanh Nguyen; Thu Ha Nguyen Thi; Hoang Sa Nguyen; Tuyen Van Nguyen

doi:10.1016/j.bmcl.2021.128054

Synthesis and biological evaluation of novel benzo[a]pyridazino[3,4-c]phenazine derivatives

Bioorg Med Chem Lett. 2021 Jul 1:43:128054. doi: 10.1016/j.bmcl.2021.128054. Epub 2021 Apr 22.

Authors

Giang Le-Nhat-Thuy¹, Tuyet Anh Dang Thi², Quynh Giang Nguyen Thi², Phuong Hoang Thi³, Tuan Anh Nguyen³, Ha Thanh Nguyen³, Thu Ha Nguyen Thi³, Hoang Sa Nguyen⁴, Tuyen Van Nguyen⁵

Affiliations

¹ Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: lenhatthuygiang@yahoo.com.
² Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
³ Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
⁴ University of Khanh Hoa, 1 Nguyen Chanh, Nhatrang, Khanhhoa, Viet Nam.
⁵ Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: ngvtuyen@hotmail.com.

PMID: 33895275
DOI: 10.1016/j.bmcl.2021.128054

Abstract

A convenient microwave-assisted one-pot four-component synthetic approach was developed en route to novel functionalized benzo[a]pyridazino[3,4-c]phenazine derivatives starting from 2-hydroxy-1,4-naphthoquinone, aromatic aldehydes, methyl hydrazine and o-phenylenediamine. Nine new derivatives were successfully synthesized and subsequently evaluated in terms of their biological profiles. The results revealed good cytotoxic activities of compounds 6a, 6h against KB, HepG2, Lu1 and MCF7 human cancer cell lines. Besides that, compound 6d exhibited promising antimicrobial activities toward Staphylococcuc aureus and Bacillus subtilis bacterial strains with IC₅₀ < 6 μM.

Keywords: 2-Hydroxy-1,4-naphthoquinone; 4-c]Phenazines; Antimicrobial activity; Benzo[a]pyridazino[3,4-c]phenazines; Cytotoxicity; Multicomponent reactions.

Publication types

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

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bacillus subtilis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Microbial Sensitivity Tests
Molecular Structure
Phenazines / chemical synthesis
Phenazines / chemistry
Phenazines / pharmacology*
Pyridazines / chemical synthesis
Pyridazines / chemistry
Pyridazines / pharmacology*
Staphylococcus aureus / drug effects*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antineoplastic Agents
Phenazines
Pyridazines