Investigation of the Cytotoxic Potencies of substituted dipyrrolo[1,2-a:2',1'-c]pyrazines and substituted pyrrolo[2'',1'':3',4']pyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-8(9H)-ones

Barghi Lish, Azam; Kolvari, Eskandar; Foroumadi, Alireza; Koukabi, Nadiya

doi:10.22075/chem.2024.34180.2272

Investigation of the Cytotoxic Potencies of substituted dipyrrolo[1,2-a:2',1'-c]pyrazines and substituted pyrrolo[2'',1'':3',4']pyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-8(9H)-ones

Document Type : Original Article

Authors

Azam Barghi Lish ¹

Eskandar Kolvari ¹

Alireza Foroumadi ²

Nadiya Koukabi ¹

¹ Faculty of Chemistry, Semnan University, Semnan, Iran

² Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

10.22075/chem.2024.34180.2272

Abstract

Cancer is the world's second leading cause of death after cardiovascular diseases. The data reported by the World Health Organization (WHO) about this disease indicates a troubling increase in both prevalence and mortality over the past decade. Consequently, significant efforts have been directed toward the discovery and development of a new and potent anticancer agents. In an attempt to find and develop further new compounds possessing cytotoxic potencies, the efficient, simple, and multi-step synthetic routes were employed to afford various substituted dihydrodipyrrolo[1,2-a:2',1'-c]pyrazine-2,3-dicarboxylates 8a-8s, which were subsequently subjected to cyclization in the presence of hydrazine hydrate to produce tetrahydropyrrolo[2'',1'':3',4']pyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-8(9H)-ones 10a-10q. Afterwards, their cytotoxicity were examined against five human cancerous cell lines, including MCF7, HeLa, SW480, HepG2, and A549 by using the MTT colorimetric assay. Considering the results, further evaluations were conducted on the compound 8l, which exhibited the induction of apoptosis and G0 cell cycle arrest in MCF7 and A549 cells.

Keywords

: pyrrolo[1

2-a]pyrazine

6-dihydropyrrolo[1

2-a:2'

1'-c]pyrazine

cancer

N-aminoethylpyrrole

aryl glyoxal

dimethyl acetylenedicarboxylate

Subjects